IndraLab

Statements

OTUD3 is modified
1 | 2 63 3
OTUD3 is acetylated.
| 48
OTUD3 is acetylated. 10 / 34
| 34
sparser
"These data indicate that CBP linked the glucose and fatty acid overload with OTUD3 acetylation status ( Figure 6 H)."
35675826
sparser
"Acetylation of OTUD3 significantly enhances its activity in forming Lys63 linkages on MAVS, and acetylation can promote ubiquitination of p62 [ xref , xref ]."
38326336
sparser
"As the full activation of OTUD3 may require its acetylation xref , xref , it will be interesting to determine whether OTUD3 acetylation is also involved in PTEN regulation."
36385557
sparser
"We found that OTUD3 acetylation levels were decreased significantly when nine lysine residues were replaced with arginine (9KR) ( Figure S7 J, lane 4 versus lane 3 and lane 2 versus lane 1)."
35675826
sparser
"In metabolism, OTUD3 acetylation promotes its nuclear translocation, where it modulates transcriptional programs related to lipid and glucose homeostasis."
41437362
sparser
"These findings illustrate that OTUD3 sits at the intersection of inflammation and metabolism: inflammatory conditions can alter metabolic gene expression via OTUD3, and conversely, metabolic stressors such as a high-fat diet can modulate OTUD3 acetylation and nuclear translocation [ xref ], affecting inflammatory gene expression."
41437362
sparser
"We further demonstrated that the CBP acetyltransferase, a crucial cofactor in the regulation of energy homeostasis through its acetyltransferase activity, regulates the acetylation and translocation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
sparser
"We found that both glucose and FFA significantly increased OTUD3 acetylation levels in a dose-dependent manner ( Figure 6 C, lanes 2–4 versus lane 1; Figure S7 C, lanes 2–4 versus lane 1)."
35675826
sparser
"OTUD3 is a deubiquitinase dependent on its Lys129-acetylation, and acetylated OTUD3 hydrolyzes polyubiquitination of Lys63 on MAVS during resting state."
37829187
sparser
"ACLY inhibitor SB 204990 remarkably attenuated both glucose- and FFA-stimulated OTUD3 acetylation ( Figures 6 C and S7 C, lanes 6–8 versus lanes 2–4)."
35675826
OTUD3 is acetylated on K129. 10 / 14
| 14
sparser
"Although we have not systematically investigated the stoichiometry, we found that Lys129 acetylation of OTUD3 occurred more efficiently in innate immune cells and lymphocytes."
32679077
sparser
"To confirm that OTUD3 was acetylated at Lys129, we generated an antibody specific for Lys129-acetylated OTUD3."
32679077
sparser
"Intriguingly, OTUD1 with a corresponding amino acid, Gln, possesses a very strong capacity to cleave Lys63-linked Ub chain, while OTUD2 with a corresponding amino acid, Arg, shows absolutely no affini[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"To unambiguously determine the effect of acetylation on OTUD3, we utilized genetic code expansion orthogonal systems ( Neumann et al., 2008 ; Ryu and Schultz, 2006 ) to incorporate acetyl-lysine into [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
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."
33511009
sparser
"As expected, antibodies specific for Lys129-acetylated OTUD3 could detect OTUD3 Lys129-Ac but not OTUD3 Non-Ac ( Figure 5 K)."
32679077
sparser
"We found that OTUD3 Lys129-Ac was rather efficient in an Ub-AMC assay, while the OTUD3 Non-Ac was much less active in cleaving Ub-AMC in vitro ( Figure 5 L), indicating the Lys129-acetylated OTUD3 is [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"We found that cells treated with sirtuin inhibitor NAM, but not the HDAC inhibitor Trichostatin A (TSA), exhibited increased Lys129 acetylation of endogenous OTUD3 ( Figure 6 A)."
32679077
sparser
"OTUD3 that is acetylated at Lys129 (acetyl-Lys129 OTUD3) shows markedly enhanced affinity to Lys63 linkage on MAVS."
32679077
sparser
"NAM treatment also elevated Lys129 acetylation of ectopic expressed OTUD3 and nearly completely blocked virus-induced deacetylation of OTUD3 ( Figure 6 B), indicating sirtuins might be involved in dea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 is phosphorylated.
1 | 12 3
OTUD3 is phosphorylated. 9 / 9
| 9
sparser
"Crucially, Ser9 is essential for this function: GSK3β activation increased phosphorylation of wild-type OTUD3, but not an S9A mutant, while treatment with GSK3β inhibitors such as Tideglusib disrupted this axis."
41437362
sparser
"Then, we further explored the functions of PLK1 in OTUD3 phosphorylation."
38351178
sparser
"Identification of OTUD3 phosphorylation by PLK1 adds a new layer of complexity to regulation of this signaling pathway and highlights the importance of phosphorylation in regulation of DUBs (Fig. xref )."
38351178
sparser
"Pretreatment with the PLK1-specific inhibitor, HMN-214 (3 μM, 6 h), significantly inhibited OTUD3 phosphorylation (Fig. xref and Supplementary Fig. xref )."
38351178
sparser
"Furthermore, EX527 repressed SeV-induced MAVS aggregation and the downstream signaling events, including IRF3 dimer formation and the phosphorylation of TBK1 and IRF3, in Otud3 +/+ but not Otud3 −/− M[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"Additional experiments showed that PLK1 failed to phosphorylate OTUD3 with Ser-326A mutations (Fig. xref )."
38351178
sparser
"In summary, phosphorylation of the OTUD3 protein enhances its ability to bind YY1, ultimately further maintaining YY1 protein stability."
38351178
sparser
"We found that PLK1 mediates OTUD3 phosphorylation to enhance its binding abilities, resulting in YY1 stability."
38351178
sparser
"We found that OTUD3 was also phosphorylated."
38351178
OTUD3 is phosphorylated on S326. 2 / 2
| 2
sparser
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
sparser
"Phosphorylation status also affects transcriptional regulation, such as PLK1-mediated Ser326 phosphorylation of OTUD3, which stabilizes YY1 and supports tumor growth [ xref ], or the downregulation of PCYT2, which reduces YAP1 phosphorylation, enhancing metastasis through SNAIL2 and ZEB1 activation [ xref ]."
41359051
OTUD3 is phosphorylated on S20. 2 / 2
| 2
rlimsp
"Ser20 phosphorylation increased OTUD3-mediated cleavage of K11-linked Ub, but it decreased OTUD3-mediated cleavage of K48 linkage (Figure 6I)."
27425610
rlimsp
"The cleavage of K11-linked Ub dimers by OTUD3 was activated by phosphorylation of Ser20 in Ub, but it was inhibited by phosphorylation at Ser57 or Ser65 (Figure 5C)."
27425610
OTUD3 is phosphorylated on S9. 1 / 1
| 1
sparser
"GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
OTUD3 is phosphorylated on S65. 1 / 1
| 1
rlimsp
"The cleavage of K11-linked Ub dimers by OTUD3 was activated by phosphorylation of Ser20 in Ub, but it was inhibited by phosphorylation at Ser57 or Ser65 (Figure 5C)."
27425610
OTUD3 is phosphorylated on S224. 1 / 1
1 |
hprd
No evidence text available
18669648
OTUD3 is ubiquitinated.
| 1 1
OTUD3 is ubiquitinated. 2 / 2
| 1 1
reach
"We speculate that the balance between the Mdm2-mediated ubiquitination and OTUD3-mediated deubiquitination of p53 is critical for p53 stabilization."
32571254
sparser
"We further confirmed that ectopic expression of OTUD3 did not impair K48-linked ubiquitination of OTUD3 (K279R) ( Figure 7 R)."
35675783
OTUD3 is methylated.
| 2
OTUD3 is methylated. 2 / 2
| 2
sparser
"Methylation in the OTUD3 gene has previously been associated with glucocorticoid exposure [ xref ]."
36457109
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)."
32571254
OTUD3 is deubiquitinated.
| 1
OTUD3 is deubiquitinated. 1 / 1
| 1
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
OTUD3 affects HSPA5
4 | 1 29 30
OTUD3 binds HSPA5.
4 | 4 30
OTUD3 binds HSPA5. 10 / 38
4 | 4 30
sparser
"Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis."
38539203
sparser
"In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer."
38539203
sparser
"Given that OTUDin3 binds to the OTU domain, we further investigated whether OTUDin3 disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST-pulldown assays."
37369659
sparser
"Co-IP and GST-pulldown assays confirmed that OTUDin3 did not affect the interaction between OTUD3 and GRP78 (Fig. xref , Supplementary Fig. xref )."
37369659
biogrid
No evidence text available
31266968
biogrid
No evidence text available
31266968
sparser
"In addition, a study on CHIP, an E3 ubiquitin ligase for OTUD3, further confirmed that OTUD3 promoted NSCLC through an OTUD3-GRP78 signaling axis [ xref ]."
37369659
sparser
"In our present study, we identified Rolapitant as an inhibitor of OTUD3 that can also promote ER stress DR5-induced apoptosis of lung cancer cells through disrupting the interaction of OTUD3 with GRP78."
38539203
sparser
"Besides, rolapitant may trigger the ER stress-CHOP-DR5 signaling pathway by targeting the OTUD3-GRP78 axis, enhancing TRAIL induced apoptosis in lung cancer cells ( xref )."
40978046
biogrid
No evidence text available
31266968
OTUD3 activates HSPA5.
| 1 10
OTUD3 activates HSPA5. 10 / 11
| 1 10
reach
"The result was consistent with the downregulation of GRP78 by OTUD3 knockdown in the H1299 cell line [26]."
37369659
reach
"OTUD3 upregulates GRP78 in a manner dependent on its deubiquitinating activity, as the catalytically inactive mutant C76A lost its ability to upregulate GRP78 [26]."
37369659
reach
"The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer."
37369659
reach
"OTUD3 positively regulates GRP78, which in turn promotes the growth of LUAD cells68."
34405018
reach
"OTUD3 promotes lung tumorigenesis by stabilizing GRP78 [44], while it stabilizes ACTN4 to drive hepatocellular carcinoma progression and metastasis [45]."
38351178
reach
"Our previous study indicated that deubiquitinase OTUD3 promoted the progression of lung cancer through stabilizing GRP78 [2]."
38539203
eidos
"As OTUD3 binds to and positively regulate GRP78 protein stability , we hypothesized that OTUD3 might increase GRP78 expression via deubiquitylation of GRP78 ."
31266968
reach
"Our previous study confirmed that OTUD3 promotes lung tumorigenesis by stabilizing the substrate GRP78 [2]."
38539203
reach
"The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer."
38539203
reach
"In contrast to the downregulation of GRP78 stability and the suppression of tumor metastasis by GP78, OTUD3 enhances GRP78 stability, leading to the growth of lung cancer cells and contributing to tumorigenesis [54, 55]."
35661704
OTUD3 inhibits HSPA5.
| 4
OTUD3 inhibits HSPA5. 4 / 4
| 4
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"Western blotting analysis showed that OTUDin3 downregulated GRP78 in a time-dependent manner, and the downregulation effect was significant after 24 h (Fig. 4A)."
37369659
reach
"Then, H1299 cells were treated with increasing concentrations of OTUDin3 for 24 h. Western blotting analysis showed that OTUDin3 downregulated GRP78 in a concentration-dependent manner without affecting the stability of OTUD3 (Fig. 4B)."
37369659
reach
"OTUDin3 enhanced degradation of the substrate GRP78 by inhibiting the deubiquitinating activity of OTUD3."
37369659
reach
"OTUDin3 downregulates GRP78 by inhibiting the deubiquitinating activity of OTUD3."
37369659
OTUD3 deubiquitinates HSPA5.
| 4
OTUD3 deubiquitinates HSPA5. 3 / 3
| 3
reach
"Mechanistic studies indicated that OTUD3 promoted lung tumorigenesis by deubiquitylating and stabilizing GRP78 [26]."
37369659
reach
"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."
33743739
reach
"The results showed that overexpression of OTUD3 significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant OTUD3 did not reduce the level of GRP78 ubiquitination."
37369659
Mutated OTUD3 leads to the deubiquitination of HSPA5. 1 / 1
| 1
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"The results showed that overexpression of OTUD3 significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant OTUD3 did not reduce the level of GRP78 ubiquitination."
37369659
OTUD3 decreases the amount of HSPA5.
| 4
OTUD3 decreases the amount of HSPA5. 3 / 3
| 3
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"The results showed that overexpression of OTUD3 significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant OTUD3 did not reduce the level of GRP78 ubiquitination."
37369659
reach
"A GRP78 ubiquitylation assay showed that overexpression of OTUD3 WT significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant C76A did not reduce the level of GRP78 ubiquitination (Fig. 3D)."
38539203
reach
"These data suggested that OTUD3 knockdown-induced ER stress did not affect the protein expression of Bip in the SN of mice, which might be related to the fact that the function of OTUD3 is tissue-dependent."
37107185
Mutated OTUD3 decreases the amount of HSPA5. 1 / 1
| 1
reach
"The results showed that overexpression of OTUD3 significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant OTUD3 did not reduce the level of GRP78 ubiquitination."
37369659
OTUD3 increases the amount of HSPA5.
| 2
OTUD3 increases the amount of HSPA5. 2 / 2
| 2
reach
"Based on our data, we propose that Rolapitant directly inhibit the deubiquitinating activity of OTUD3 through binding to OTUD3 to cause the downregulation of GRP78 protein levels."
38539203
reach
"Knockdown of CHIP stabilizes OTUD3 which leads to elevated GRP78 levels in lung cancer cells."
32483383
OTUD3 ubiquitinates HSPA5.
| 1
OTUD3 leads to the ubiquitination of HSPA5. 1 / 1
| 1
reach
"A GRP78 ubiquitylation assay showed that overexpression of OTUD3 WT significantly reduced the level of GRP78 ubiquitination, and the catalytically inactive mutant C76A did not reduce the level of GRP78 ubiquitination (Fig. 3D)."
38539203
OTUD3 affects PTEN
1 5 1 | 1 17 27 1
OTUD3 binds PTEN.
5 | 5 27
PTEN binds OTUD3. 10 / 37
5 | 5 26
sparser
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer ( xref )."
37829187
sparser
"OTUD3 interacts with PTEN, removing its polyubiquitination and promoting its stability."
38288086
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 ."
31266968
reach
"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."
26657567
sparser
"Early evidence suggests that OTUD3 functions as a deubiquitinase for PTEN, interacting with PTEN to enhance its stability, thus inhibiting the progression of breast cancer [ xref ]."
39097608
sparser
"Studies have reported that downregulation of miR-520h contributes to anticancer activity in human breast cancer and human cervical cancer cell lines [ xref ]; miR-520h promotes drug resistance to paclitaxel by targeting OTUD3-PTEN axis in breast cancer [ xref ]; miR-520h overcomes bortezomib resistance in multiple myeloma via suppressing APE1 [ xref ]."
34516353
reach
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer (Yuan et al., 2015)."
37829187
reach
"OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN."
26280536
sparser
"Similarly, the deubiquitylase OTUD3 can interact with PTEN and deubiquitinate it, thus stabilising PTEN and inhibiting the development of breast cancer ( xref )."
36969062
biogrid
No evidence text available
26280536
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."
32140262
OTUD3 deubiquitinates PTEN.
1 1 | 6
OTUD3 deubiquitinates PTEN. 7 / 7
1 | 6
reach
"It is worth mentioning that OTUD3 is decreased in breast cancer and suppresses tumorigenesis by deubiquitinating PTEN 70."
34405018
ubibrowser
"Here, we report <span class="match term0">OTUD3</span> as a deubiquitylase of <span class="match term1">PTEN</span>. <span class="match term0">OTUD3</span> interacts with, de-polyubiquitylates and stabilizes <span class="match term1">PTEN</span>."
26280536
reach
"OTUD3 (OTU region) directly interacts with PTEN (C2 domain), deubiquitinating and stabilizing the PTEN protein to suppress PI3K-AKT signaling ."
36385557
reach
"Our previous results showed that OTUD3 can deubiquitinate and stabilize PTEN."
32571254
reach
"Notably, Zhao et al (90) discovered that in thyroid carcinoma, OTUD3 deubiquitinates PTEN, thereby increasing PTEN protein stability and inhibiting the activation of PI3K/AKT signaling."
40337608
reach
"PTEN is ubiquitinated by WWP2 and NEDD4 [ 49 , 50 ] and is deubiquitinated by USP13 and OTUD3 [ 19 , 20 ]."
29331416
reach
"OTUD3 could deubiquitylate and stabilize the tumor suppressor PTEN in breast cancer at the protein level."
38539203
OTUD3 deubiquitinates PTEN on lysine. 1 / 1
1 |
biopax:reactome
No evidence text available
OTUD3 inhibits PTEN.
| 3
OTUD3 inhibits PTEN. 3 / 3
| 3
reach
"In breast cancer, OTUD3 suppresses tumorigenesis and progression by stabilizing PTEN [46]."
38351178
reach
"OTUD3 loss of function increases the Ub-dependent degradation of PTEN and enhances PI3K/AKT signaling in breast cancer cells ( Yuan et al., 2015 )."
35675826
reach
"In addition to regulating GRP78 to promote tumorigenesis in NSCLC, OTUD3 suppressed tumorigenesis in breast, colon, liver, brain, esophageal, and cervical cancer by stabilizing PTEN, ZFP36 or p53 [23–25]."
37369659
OTUD3 ubiquitinates PTEN.
| 2
OTUD3 leads to the ubiquitination of PTEN. 2 / 2
| 2
reach
"Furthermore, several DUBs, including HAUSP/USP7, USP10, USP11, USP13, OTUD3, and Ataxin-3 have been shown to reverse the ubiquitination of PTEN, a key antagonist in the PI3K growth-promoting pathway, implicating its function in cancer-specific contexts [15]."
39075050
reach
"Several studies have demonstrated that OTUD3 interacts with PTEN and induces its deubiquitination, increasing PTEN protein stability and inhibiting carcinogenic PI3K/AKT signaling (89)."
40337608
OTUD3 activates PTEN.
| 1 1
OTUD3 activates PTEN. 2 / 2
| 1 1
reach
"For example, OTUD3 promotes the progression of PTEN-associated glioma [34]."
38429268
eidos
"Depletion of OTUD3 dramatically decreased PTEN levels , and two independent OTUD3 shRNAs showed significant effects ( Supplementary Fig. 3a , b ) ."
31266968
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."
32395534
HSPA5 affects OTUD3
4 | 9 30
HSPA5 binds OTUD3.
4 | 4 30
OTUD3 binds HSPA5. 10 / 38
4 | 4 30
sparser
"Mechanistically, Rolapitant directly targeted the OTUD3-GRP78 axis to trigger endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-DR5 signaling, sensitizing lung cancer cells to TRAIL-induced apoptosis."
38539203
sparser
"In summary, the present study identifies Rolapitant as a novel inhibitor of deubiquitinase OTUD3 and establishes that the OTUD3-GRP78 axis is a potential therapeutic target for lung cancer."
38539203
sparser
"Given that OTUDin3 binds to the OTU domain, we further investigated whether OTUDin3 disrupted the interaction between OTUD3 and GRP78 by performing co-IP and GST-pulldown assays."
37369659
sparser
"Co-IP and GST-pulldown assays confirmed that OTUDin3 did not affect the interaction between OTUD3 and GRP78 (Fig. xref , Supplementary Fig. xref )."
37369659
biogrid
No evidence text available
31266968
biogrid
No evidence text available
31266968
sparser
"In addition, a study on CHIP, an E3 ubiquitin ligase for OTUD3, further confirmed that OTUD3 promoted NSCLC through an OTUD3-GRP78 signaling axis [ xref ]."
37369659
sparser
"In our present study, we identified Rolapitant as an inhibitor of OTUD3 that can also promote ER stress DR5-induced apoptosis of lung cancer cells through disrupting the interaction of OTUD3 with GRP78."
38539203
sparser
"Besides, rolapitant may trigger the ER stress-CHOP-DR5 signaling pathway by targeting the OTUD3-GRP78 axis, enhancing TRAIL induced apoptosis in lung cancer cells ( xref )."
40978046
biogrid
No evidence text available
31266968
HSPA5 ubiquitinates OTUD3.
| 2
Ubiquitinated HSPA5 leads to the ubiquitination of OTUD3. 2 / 2
| 2
reach
"However, when OTUD3 overexpressing cells were treated with OTUDin3, GRP78 ubiquitination was increased, reversing the deubiquitination of OTUD3 (Fig. 4C)."
37369659
reach
"However, when OTUD3 WT overexpressing cells were treated with Rolapitant, GRP78 ubiquitination was increased, reversing the deubiquitination of OTUD3 (Fig. 3D)."
38539203
HSPA5 deubiquitinates OTUD3.
| 2
Ubiquitinated HSPA5 leads to the deubiquitination of OTUD3. 2 / 2
| 2
reach
"However, when OTUD3 overexpressing cells were treated with OTUDin3, GRP78 ubiquitination was increased, reversing the deubiquitination of OTUD3 (Fig. 4C)."
37369659
reach
"However, when OTUD3 WT overexpressing cells were treated with Rolapitant, GRP78 ubiquitination was increased, reversing the deubiquitination of OTUD3 (Fig. 3D)."
38539203
HSPA5 inhibits OTUD3.
| 1
HSPA5 inhibits OTUD3. 1 / 1
| 1
reach
"The results indicated that OTUDin3 increased GRP78 ubiquitylation by inhibiting the deubiquitinating activity of OTUD3."
37369659
PTEN affects OTUD3
5 | 6 27
PTEN binds OTUD3.
5 | 5 27
PTEN binds OTUD3. 10 / 37
5 | 5 26
sparser
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer ( xref )."
37829187
sparser
"OTUD3 interacts with PTEN, removing its polyubiquitination and promoting its stability."
38288086
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 ."
31266968
reach
"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."
26657567
sparser
"Early evidence suggests that OTUD3 functions as a deubiquitinase for PTEN, interacting with PTEN to enhance its stability, thus inhibiting the progression of breast cancer [ xref ]."
39097608
sparser
"Studies have reported that downregulation of miR-520h contributes to anticancer activity in human breast cancer and human cervical cancer cell lines [ xref ]; miR-520h promotes drug resistance to paclitaxel by targeting OTUD3-PTEN axis in breast cancer [ xref ]; miR-520h overcomes bortezomib resistance in multiple myeloma via suppressing APE1 [ xref ]."
34516353
reach
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer (Yuan et al., 2015)."
37829187
reach
"OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN."
26280536
sparser
"Similarly, the deubiquitylase OTUD3 can interact with PTEN and deubiquitinate it, thus stabilising PTEN and inhibiting the development of breast cancer ( xref )."
36969062
biogrid
No evidence text available
26280536
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."
32140262
PTEN activates OTUD3.
| 1
PTEN activates OTUD3. 1 / 1
| 1
reach
"Indeed, HAUSP/USP7, Ataxin-3, USP10, USP11, USP13, and OTUD3 have all been identified as PTEN DUBs; HAUSP specifically removes monoubiquitin from PTEN to promote its nuclear export ; Ataxin-3 restricts PTEN transcription ; and USP10, USP11, USP13 and OTUD3 increase PTEN stability in different cancer-specific contexts ."
36385557
OTUD3 affects YY1
| 31 5
OTUD3 activates YY1.
| 13
OTUD3 activates YY1. 10 / 13
| 13
reach
"Therefore, we postulated that OTUD3 promotes CRC progression by up-regulating YY1."
38351178
reach
"Overall, these findings are in agreement with our experimental findings on OTUD3-mediated YY1 stability."
38351178
reach
"OTUD3 enhances the stability of YY1 by cleaving ubiquitin molecules from YY1 at K332, K339 and K409 residues."
38351178
reach
"Over-expression of OTUD3 suppressed YY1 degradation and promoted CRC cell growth."
38351178
reach
"Our findings suggest that OTUD3 promotes CRC progression by up-regulating YY1, and provides insights into the underlying mechanisms of YY1 over-expression in CRC."
38351178
reach
"These results suggest that OTUD3 tightly controls YY1 protein stability.Next, we investigated the downstream effects of OTUD3-mediated YY1 regulation."
38351178
reach
"We then investigated how OTUD3 enhances YY1 stability."
38351178
reach
"In summary, OTUD3 enhances YY1 stability by selectively removing K48-linked polyubiquitination chains from the YY1 protein."
38351178
reach
"OTUD3 accelerates CRC progression by up-regulating YY1."
38351178
reach
"Over-expression of OTUD3 significantly increased YY1 protein expression and suppressed its ubiquitination, whereas OTUD3 knockdown or knockout increased YY1 degradation."
38351178
OTUD3 binds YY1.
| 6 5
OTUD3 binds YY1. 10 / 11
| 6 5
sparser
"Importantly, interactions between endogenous YY1 and OTUD3 were observed in SW480, LoVo and DLD1 cells (Fig. xref and Supplementary Fig. xref )."
38351178
sparser
"OTUD3 directly binds to and deubiquitinates YY1, preventing its proteasomal degradation."
41437362
sparser
"Notably, the OTUD3-YY1 axis provides a compelling link between inflammatory signals and CRC progression, consistent with YY1 upregulation in inflammation-associated cancers [ xref ]."
41437362
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
reach
"Importantly, interactions between endogenous YY1 and OTUD3 were observed in SW480, LoVo and DLD1 cells (Fig. 1C and Supplementary Fig. S1B)."
38351178
reach
"Furthermore, in vitro pull-down assays with purified recombinant proteins showed that YY1 directly bound GST-OTUD3, not GST control (Fig. 1D)."
38351178
reach
"An in-situ proximity ligation assay (PLA) was performed to identify the interactions between endogenous YY1 and OTUD3 in CRC cells."
38351178
reach
"Then, the immunoprecipitation assays confirmed that up-regulated PLK1 promoted the physical binding between OTUD3 and YY1, but failed to promote the binding between OTUD3 mutation (S326A) and YY1 (Fig. 5L–N and Supplementary Fig. S5A, B)."
38351178
sparser
"We found that OTUD3 directly interacts with YY1."
38351178
sparser
"OTUD3 interacts with YY1."
38351178
OTUD3 deubiquitinates YY1.
| 6
OTUD3 deubiquitinates YY1. 5 / 5
| 5
reach
"OTUD3 deubiquitinates YY1."
38351178
reach
"Conversely, over-expression of wild-type OTUD3 dose-dependently suppressed YY1 polyubiquitination in DLD1 cells and HEK-293T cells (Fig. 3A, B)."
38351178
reach
"Moreover, consistent with these findings, up-regulation of PLK1 promoted the deubiquitination of YY1 by OTUD3 (wild-type), while OTUD3-S326A weakened the deubiquitination of YY1, compared to OTUD3(wild-type) (Fig. 5S, T)."
38351178
reach
"In this study, we found that OTUD3 can promote YY1 protein deubiquitination and stabilization."
38351178
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
OTUD3-C76A leads to the deubiquitination of YY1. 1 / 1
| 1
reach
"In vitro deubiquitylation assays showed that wild-type OTUD3, but not the OTUD3-C76A mutant, suppressed YY1 ubiquitination (Fig. 3D)."
38351178
OTUD3 increases the amount of YY1.
| 3
OTUD3 increases the amount of YY1. 3 / 3
| 3
reach
"Over-expression of OTUD3 significantly increased YY1 protein expression and suppressed its ubiquitination, whereas OTUD3 knockdown or knockout increased YY1 degradation."
38351178
reach
"Ectopic expression of wild-type OTUD3, instead of the catalytically inactive mutant OTUD3-C76A, increased YY1 protein levels (Fig. 2E, F)."
38351178
reach
"Similarly, in OTUD3 knockout SW480 cells (generated using CRISPR/Cas9), ectopic expression of wild-type OTUD3, instead of mutant OTUD3, restored YY1 protein levels (Fig. 2G)."
38351178
OTUD3 ubiquitinates YY1.
| 1
OTUD3 leads to the ubiquitination of YY1. 1 / 1
| 1
reach
"In vitro deubiquitylation assays showed that wild-type OTUD3, but not the OTUD3-C76A mutant, suppressed YY1 ubiquitination (Fig. 3D)."
38351178
OTUD3 inhibits YY1.
| 1
OTUD3 inhibits YY1. 1 / 1
| 1
reach
"It was found that OTUD3 significantly reduced the ubiquitination of lys-332, lys-339, and lys-409 of YY1, and slightly up-regulated the ubiquitination of lys-393 (Supplementary Fig. S3E)."
38351178
OTUD3 decreases the amount of YY1.
| 1
OTUD3 decreases the amount of YY1. 1 / 1
| 1
reach
"Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC)."
38351178
OTUD3 affects TP53
4 1 | 17 13 1
OTUD3 binds TP53.
4 | 6 13 1
TP53 binds OTUD3. 10 / 23
4 | 6 13
sparser
"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."
32571254
reach
"OTUD3 can directly interact with and stabilize p53 through deubiquitination in BC cells."
32571254
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."
32571254
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."
32571254
sparser
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
32571254
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)."
32571254
sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."
32571254
sparser
"Interestingly, Myc-D1 cultured from MCF7 cells was specifically bound by the purified GST-TP53 protein but not GST alone (Fig. xref e), further illustrating the direct interaction between OTUD3 and p53."
32571254
sparser
"To determine the region where p53 binds OTUD3, we also constructed truncated p53 mutants (Fig. xref f) and performed GST assays."
32571254
sparser
"The results indicated that OTUD3 bound the following two mutants of p53: T2 (1–113)/(290–393) and T3 (1–113)/(236–393) (Fig. xref g, h)."
32571254
OTUD3 binds TP53. 1 / 1
| 1
isi
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
32571254
OTUD3 deubiquitinates TP53.
1 | 6
OTUD3 deubiquitinates TP53. 7 / 7
1 | 6
reach
"OTUD3 deubiquitinates p53."
32571254
reach
"As OTUD3 is a deubiquitinase, we examined whether OTUD3 deubiquitinates p53."
32571254
reach
"Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells."
32571254
reach
"OTUD3 likely deubiquitinates p53 to counteract the action of the E3 ubiquitin ligase Mdm2."
32571254
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)."
32571254
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."
32571254
ubibrowser
"Tumor suppressor <span class="match term0">OTUD3</span> induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing <span class="match term1">p53</span> in invasive breast carcinoma cells"
32571254
OTUD3 ubiquitinates TP53.
| 2
OTUD3 ubiquitinates TP53. 2 / 2
| 2
reach
"In contrast, the OTUD3 downregulation by shRNA increased p53 ubiquitination in the MCF7 and DU4475 cells (Fig. 5b)."
32571254
reach
"Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells."
32571254
OTUD3 inhibits TP53.
| 2
OTUD3 inhibits TP53. 2 / 2
| 2
reach
"In addition to regulating GRP78 to promote tumorigenesis in NSCLC, OTUD3 suppressed tumorigenesis in breast, colon, liver, brain, esophageal, and cervical cancer by stabilizing PTEN, ZFP36 or p53 [23–25]."
37369659
reach
"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."
32571254
OTUD3 activates TP53.
| 1
OTUD3 activates TP53. 1 / 1
| 1
reach
"These results demonstrate that OTUD3 can antagonize the reduction in p53 by Mdm2."
32571254
OTUD3 affects IREB2
3 | 14 10
OTUD3 binds IREB2.
3 | 2 8
OTUD3 binds IREB2. 10 / 13
3 | 2 8
sparser
"Co-IP further confirmed the interaction between OTUD3 and IRP2 (Fig.  xref C)."
39415292
sparser
"These findings position the OTUD3-IRP2 axis as a promising therapeutic target for preventing iron-mediated neurodegeneration in PD, offering a novel approach to modify disease progression by maintaining proper iron homeostasis."
41204197
reach
"Co-IP further confirmed the interaction between OTUD3 and IRP2 (Fig. 2C)."
39415292
reach
"Subsequently, the interaction between OTUD3 and IRP2 was determined."
35490179
sparser
"OTUD3, a deubiquitinating enzyme of IRP2, interacts with IRP2 in the cytoplasm, and deubiquitinates and stabilizes the IRP2 protein in an iron-independent manner."
39415292
biogrid
No evidence text available
35490179
sparser
"The functional significance of the OTUD3-IRP2 axis is particularly evident in pathological states."
41437362
sparser
"Subsequently, the interaction between OTUD3 and IRP2 was determined."
35490179
sparser
"In line with this, hou et al. further broader significance of the OTUD3-IRP2 axis in PD iron homeostasis (Hou et al. xref )."
41204197
biogrid
No evidence text available
35490179
OTUD3 increases the amount of IREB2.
| 7 2
OTUD3 increases the amount of IREB2. 9 / 9
| 7 2
reach
"In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"These evidences suggest that OTUD3 knockout may induce ER stress by reducing the expression of IRP2 protein and up-regulating the contents of iron in neurons."
37107185
sparser
"In addition, OTUD3 induced IRP2 expression to protect damaged hippocampal neurons."
39415292
reach
"Overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Overexpression of an siRNA-resistant WT OTUD3, rather than the C76A mutant, reversed the decrease of IRP2 levels induced by OTUD3 knockdown (Fig. 3d)."
35490179
reach
"These results suggested that the overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Finally, through in vivo experimental verification, we verified the mechanism of this new pathway in IS; namely, overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway.In conclusion, we preliminarily evaluated the effects of the OTUD3/IRP2/p53/PTGS2 pathway on IS and determined whether its potential mechanism of action was related to ferroptosis."
39415292
sparser
"OTUD3 induced IRP2 expression to protect damaged hippocampal neurons."
39415292
reach
"OTUD3 promoted IRP2 expression to protect damaged hippocampal neurons."
39415292
OTUD3 inhibits IREB2.
| 2
OTUD3 inhibits IREB2. 2 / 2
| 2
reach
"The deubiquitinase OTUD3 prevents Parkinson’s disease by stabilizing IRP2 [17]."
39415292
reach
"In addition, OTUD3 prevented Parkinson’s disease (PD) by stabilizing iron regulatory protein 2 [28]."
37369659
OTUD3 decreases the amount of IREB2.
| 2
OTUD3 decreases the amount of IREB2. 2 / 2
| 2
reach
"Overexpression of an siRNA-resistant WT OTUD3, rather than the C76A mutant, reversed the decrease of IRP2 levels induced by OTUD3 knockdown (Fig. 3d)."
35490179
reach
"OTUD3 deletion induced disorder of iron metabolism and reduced IRP2 protein levels."
35490179
OTUD3 ubiquitinates IREB2.
| 1
OTUD3 leads to the ubiquitination of IREB2. 1 / 1
| 1
reach
"Overexpression of OTUD3 decreased IRP2 ubiquitylation induced by its E3 ligase HOIL-1 or FBXL5, although FBXL5 could induce stronger ubiquitylation of IRP2 than HOIL-1 (Supplementary Fig. 7a, b)."
35490179
TP53 affects OTUD3
4 | 6 13 1
TP53 binds OTUD3. 10 / 23
4 | 6 13
sparser
"The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments."
32571254
reach
"OTUD3 can directly interact with and stabilize p53 through deubiquitination in BC cells."
32571254
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."
32571254
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."
32571254
sparser
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
32571254
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)."
32571254
sparser
"To determine whether the OTUD3-TP53 interaction was direct, we generated and purified recombinant Myc-OTUD3, Myc-D1 and Myc-D2."
32571254
sparser
"Interestingly, Myc-D1 cultured from MCF7 cells was specifically bound by the purified GST-TP53 protein but not GST alone (Fig. xref e), further illustrating the direct interaction between OTUD3 and p53."
32571254
sparser
"To determine the region where p53 binds OTUD3, we also constructed truncated p53 mutants (Fig. xref f) and performed GST assays."
32571254
sparser
"The results indicated that OTUD3 bound the following two mutants of p53: T2 (1–113)/(290–393) and T3 (1–113)/(236–393) (Fig. xref g, h)."
32571254
OTUD3 binds TP53. 1 / 1
| 1
isi
"Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region."
32571254
PLK1 affects OTUD3
| 11 11
PLK1 binds OTUD3.
| 3 8
OTUD3 binds PLK1. 10 / 10
| 2 8
sparser
"These results indicate that OTUD3 interacted with PLK1, and PLK1‐T2 (36–305) is the sequence of PLK1 that binds to OTUD3."
40462502
sparser
"We next used co‐immunoprecipitation and western blot methods to analyse the specific fragments of OTUD3 and PLK1 that bind to each other."
40462502
sparser
"To explore the regions responsible for the interactions between OTUD3 and PLK1, we generated a set of deletion mutants of PLK1."
38351178
sparser
"In previous studies, PLK1 was shown to be involved in ferroptosis in tumour cells and played a key role in promoting tumour cell growth. xref We predicted the binding of OTUD3 and PLK1 proteins using molecular docking techniques."
40462502
sparser
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
sparser
"Binding of OTUD3 to PLK1."
40462502
reach
"In vitro pull-down assays with purified recombinant proteins showed that Myc-PLK1 directly bound GST-OTUD3, instead of GST control (Fig. 5G)."
38351178
reach
"To explore the regions responsible for the interactions between OTUD3 and PLK1, we generated a set of deletion mutants of PLK1."
38351178
sparser
"Dysregulation of its activity not only directly leads to chromosomal segregation errors and micronucleus formation but may also exacerbate oncogenic risk by interfering with DNA damage repair pathways, making it a highly promising molecular target in cancer therapy. xref , xref , xref Co‐immunoprecipitation and mass spectrometry showed that OTUD3 interacted with PLK1 and then truncated PLK1 into three parts."
40462502
sparser
"Ectopically expressed HA-tagged OTUD3 also interacted with Myc-tagged PLK1 in HEK-293T cells, and vice versa (Fig. xref and Supplementary Fig. xref )."
38351178
PLK1 binds OTUD3 and PBD domain. 1 / 1
| 1
reach
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
PLK1 phosphorylates OTUD3.
| 5 3
PLK1 phosphorylates OTUD3. 5 / 5
| 3 2
reach
"We found that PLK1 mediates OTUD3 phosphorylation to enhance its binding abilities, resulting in YY1 stability.In this study, OTUD3 was identified to be an effective DUB for de-polyubiquitination of YY1."
38351178
sparser
"In vitro kinase assays showed that OTUD3 protein was phosphorylated by Myc-PLK1 protein that were purified from HEK-293T cells (Fig. xref )."
38351178
reach
"Additional experiments showed that PLK1 failed to phosphorylate OTUD3 with Ser-326A mutations (Fig. 5J)."
38351178
sparser
"Identification of OTUD3 phosphorylation by PLK1 adds a new layer of complexity to regulation of this signaling pathway and highlights the importance of phosphorylation in regulation of DUBs (Fig. xref )."
38351178
reach
"Identification of OTUD3 phosphorylation by PLK1 adds a new layer of complexity to regulation of this signaling pathway and highlights the importance of phosphorylation in regulation of DUBs (Fig. 6I)."
38351178
PLK1 phosphorylates OTUD3 on S326. 3 / 3
| 2 1
reach
"Moreover, PLK1 phosphorylates Ser-326 of OTUD3, thereby promoting the binding and stabilization of YY1."
38351178
sparser
"Moreover, PLK1 phosphorylates Ser-326 of OTUD3, thereby promoting the binding and stabilization of YY1."
38351178
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
PLK1 activates OTUD3.
| 2
PLK1 activates OTUD3. 2 / 2
| 2
reach
"PLK1 mediated Ser-326 phosphorylation significantly enhances OTUD3 functions on YY1."
38351178
reach
"Over-expressed PLK1 enhanced the effects of OTUD3 on extending the half-life of YY1."
38351178
PLK1 dephosphorylates OTUD3.
| 1
PLK1 leads to the dephosphorylation of OTUD3. 1 / 1
| 1
reach
"Pretreatment with the PLK1-specific inhibitor, HMN-214 (3 μM, 6 h), significantly inhibited OTUD3 phosphorylation (Fig. 5I and Supplementary Fig. S4K–L)."
38351178
OTUD3 inhibits cell population proliferation. 10 / 13
| 13
reach
"OTUD3 inhibits BC cell proliferation and makes BC cells more sensitive to chemotherapeutic drug-induced apoptosis by directly interacting with p53 through the amino-terminal OTU region to deubiquitinate it from murine double minute 2 (Mdm2)-mediated ubiquitination and degradation (Pu et al., 2020)."
37829187
reach
"OTUD3 inhibits cell proliferation."
32571254
reach
"Compared to the control cells, knockdown of endogenous OTUD3 by shRNA in the MCF7 and DU4475 cells increased the cell proliferation rate."
32571254
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)."
32571254
reach
"3.6 OTUD3 suppressed proliferation and growth of HeLa by downregulating the mTORC1."
38288086
reach
"These data suggest that OTUD3 can inhibit BC cell proliferation."
32571254
reach
"These experiments collectively confirmed that OTUD3 can suppress the growth and proliferation of tumor cells.Moreover, to corroborate these findings, we conducted CCK8 cell proliferation assays on HeLa-WT, OTUD3-GFP, OTUD3-KO, OTUD3-KO cells with exogenous expression of wild-type OTUD3 (OTUD3-KO+OTUD3-Myc), and OTUD3-KO cells with exogenous expression of catalytically inactive OTUD3 (OTUD3-KO+OTUD3-C76A-Myc)."
38288086
reach
"The results revealed that stable expression of OTUD3 inhibited HeLa cell proliferation, OTUD3 knockout promoted proliferation, and reintroduction of wild-type OTUD3 into OTUD3-KO cells restored the enhanced proliferation ability."
38288086
reach
"3.7 OTUD3 suppressed proliferation and growth of HeLa by downregulating mTOR signaling mediated cell metabolism."
38288086
reach
"These results collectively support OTUD3’s ability to suppress tumor cell growth and proliferation through the downregulation of the mTOR signaling pathway."
38288086
reach
"Similarly, MicroRNA 32 (miR-32) can directly target the 3′-untranslated region (3′-UTR) of OTUD3 to inhibit OTUD3 expression, which can promote proliferation and motility of colon cancer cells and inhibits apoptosis (Jin et al., 2019)."
37829187
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."
34815255
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)."
32571254
reach
"As OTUD3 plays a promoting role in lung tumorigenesis by stabilizing GRP78, inhibitors of OTUD3 should inhibit the proliferation of NSCLC cells [26]."
37369659
reach
"However, in lung cancer, OTUD3 promotes tumour proliferation and metastasis and inhibits apoptosis through deubiquitination of GRP78 protein and is closely related to drug resistance (163)."
36969062
reach
"The results revealed that stable expression of OTUD3 inhibited HeLa cell proliferation, OTUD3 knockout promoted proliferation, and reintroduction of wild-type OTUD3 into OTUD3-KO cells restored the enhanced proliferation ability."
38288086
reach
"Mechanistically, OTUD3 promotes the proliferation of lung adenocarcinoma through deubiquitylation and stabilization of GRP78 [2]."
38539203
reach
"Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo."
34380780
reach
"In Bronchopulmonary dysplasia (BPD) mouse, miR-34c-5p negatively targeted OTUD3 which enhanced proliferation, angiogenesis, and migration in human pulmonary microvascular endothelial cells (HPMECs) (He et al., 2023) (Figure 3A)."
37829187
OTUD3 affects MAVS
| 17 3
OTUD3 inhibits MAVS.
| 6
OTUD3 inhibits MAVS. 6 / 6
| 6
reach
"For example, OTUD3 removes K63-linked ubiquitin chains from MAVS and thereby inhibits MAVS aggregation and IFN-I signaling activation (65)."
34707613
reach
"Re-expression of OTUD3 in Otud3 −/− MEFs repressed this increased MAVS aggregation, but re-expression of OTUD3 CS expression did not ( Figure S3 D)."
32679077
reach
"All these results indicate that OTUD3 represses MAVS aggregation and thus inhibits MAVS-mediated antiviral signaling.The findings reported above raised the question of how hosts respond rapidly to vir[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
reach
"Coinciding with these observations, the overexpression of OTUD3 markedly inhibited the self-association of RIG-I and MDA5, as well as the association of MAVS with RIG-I or MDA5 ( Figures S4 E–S4H)."
35675783
reach
"In contrast, knockdown OTUD3 in HEK293T by CRISPR-Cas9 cells enhanced the self-association of RIG-I and MDA5, and the association of MAVS with RIG-I or RIG-I or MDA5 ( Figures S4 I–S4L)."
35675783
reach
"Interferon induces downregulation of CYLD to promote RIG-I K63-linked ubiquitination for its activation (132) and reduces OTUD3 expression to allow MAVS to undergo K63-linked ubiquitination and activation (158)."
35795661
OTUD3 binds MAVS.
| 3 3
OTUD3 binds MAVS. 4 / 4
| 1 3
sparser
"Furthermore, OTUD3 immunoprecipitated together with MAVS in untransfected peritoneal macrophages, BMDMs, and MEFs ( Figure 3 H), which showed that endogenous MAVS is associated with OTUD3."
32679077
sparser
"19 According to the study showing that OTUD3 associates with mitochondrial antiviral-signaling protein (MAVS) to suppress anti-RNA viral immune response, 17 we also performed coIP experiments using F[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"Interestingly, a time-course analysis of SeV infection showed that, concomitant with the increased binding of MAVS to TRIM31, the association between MAVS and OTUD3 remained actually constant ( Figure[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal ( xref )."
36505476
OTUD3-C76S binds MAVS. 1 / 1
| 1
reach
"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
OTUD3 activates MAVS.
| 5
OTUD3 activates MAVS. 5 / 5
| 5
reach
"Mechanistically, acetylation of the core OTU domain in OTUD3 markedly enhances deubiquitinase activity on MAVS (mitochondrial antiviral-signaling protein), thereby inhibiting the innate antiviral immune response."
36385557
reach
"Upon viral infection, sirtuin 1 (SIRT1) is recruited to deacetylate OTUD3, leading to the inactivation of OTUD3, which relieves MAVS suppression."
36385557
reach
"All these results indicate that OTUD3 represses MAVS aggregation and thus inhibits MAVS-mediated antiviral signaling.The findings reported above raised the question of how hosts respond rapidly to vir[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
reach
"Remarkably, acetylation of OTUD3 on lysine 129 (K129) triggers deubiquitination of K63-polyubiquitination chains on MAVS thereby blocking the antiviral response (162) (Fig. 6B)."
35764170
reach
"Upon virus infection, SIRT1 was recruited to associate and co-localize with cytoplasmic OTUD3, which deacetylated OTUD3 and led to the loss of its ability to cleave MAVS Lys63-linked Ub."
32679077
OTUD3 increases the amount of MAVS.
| 1
OTUD3 increases the amount of MAVS. 1 / 1
| 1
reach
"In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126)."
34707613
OTUD3 deubiquitinates MAVS.
| 1
OTUD3 deubiquitinates MAVS. 1 / 1
| 1
reach
"The deubiquitination of MAVS by OTUD3 can inhibit the activation of IRF3, thus blocking the innate antiviral immune response (222)."
35795579
OTUD3 decreases the amount of MAVS.
| 1
OTUD3 decreases the amount of MAVS. 1 / 1
| 1
reach
"In addition, both OTUD3 and A20 negatively regulate the IFN-mediated antiviral response by modulating the polyubiquitination level of MAVS (125, 126)."
34707613
OTUD3 affects CGAS
5 | 13 2
OTUD3 binds CGAS.
5 | 6
CGAS binds OTUD3. 9 / 9
5 | 4
reach
"At the same time, the same amount of HA-OTUD3 WT and HA-OTUD3 CA were captured in corresponding pull-down samples, meaning that more FLAG-cGAS was not pulled down due to the interaction between cGAS a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"41 OTUD3-DNA interaction can lead OTUD3 to the cytosolic DNA complex and increase the association between cGAS and OTUD3, which is in agreement with the results of cGAS proximity labeling."
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
reach
"In addition, OTUD3 C76A catalytic mutation (as FLAG-OTUD3 CA) does not obviously affect the interaction between HA-cGAS and FLAG-OTUD3 ( Figure S3 C)."
36966392
reach
"This result could partially explain the enhanced association between OTUD3 and cGAS in cells under DNA activation ( Figures 3 B and 3C), and also supports that OTUD3 can be recruited to cGAS-DNA compl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
OTUD3 binds CGAS and Lys279. 1 / 1
| 1
reach
"OTUD3 binds cGAS and targets the Lys279 site for deubiquitination of k48- and k27-linked ubiquitination, thereby enhancing cGAS protein stability and DNA binding capacity (Cai et al., 2022)."
37829187
OTUD3-C76S binds CGAS. 1 / 1
| 1
reach
"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
OTUD3 activates CGAS.
| 5 2
OTUD3 activates CGAS. 5 / 5
| 4 1
sparser
"Conversely, in antiviral immunity, OTUD3 stabilizes and activates cGAS by removing inhibitory ubiquitin chains, amplifying the cGAS-STING pathway and interferon responses."
41437362
reach
"Additionally, we found out that OTUD3 could also remove K27- and K29-linked polyUb from cGAS and elevate cGAS enzymatic activity, which are the complementary findings.Most intriguingly, we discovered [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"It is plain that cGAS has higher activity after treatment with OTUD3 WT than with OTUD3 CA ( Figures 5 A and 5B ), demonstrating that OTUD3 enhances cGAS enzymatic activity by deubiquitination.Because[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"Interestingly, the deubiquitinating enzyme OTUD3 promotes cGAS-mediated DNA sensing but inhibits RLR-mediated RNA sensing ."
37945923
reach
"Taken together, these data suggest that OTUD3 targets cGAS for deubiquitination in response to HSV-1 infection.Ectopic expression of OTUD3 increased the binding of cGAS to the DNA HSV120, a synthetic [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3-C76A activates CGAS. 1 / 1
| 1
reach
"Moreover, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs restored the stability of cGAS ( Figure 7 J)."
35675783
OTUD3 activates CGAS. 1 / 1
| 1
sparser
"Conversely, in antiviral immunity, OTUD3 stabilizes and activates cGAS by removing inhibitory ubiquitin chains, amplifying the cGAS-STING pathway and interferon responses."
41437362
OTUD3 deubiquitinates CGAS.
| 2
OTUD3 deubiquitinates CGAS. 2 / 2
| 2
reach
"However, OTUD3 WT could not deubiquitinate cGAS compared with OTUD3 CA ( Figure S4 B), which indicates OTUD3 WT cannot remove specific K27-linked polyUb of cGAS catalyzed by RNF185."
36966392
reach
"This result indicates that deubiquitination of cGAS by OTUD3 enhances the DNA-binding ability of cGAS."
36966392
MYC affects OTUD3
| 19
MYC binds OTUD3.
| 18
OTUD3 binds MYC. 10 / 18
| 18
sparser
"To confirm this interaction, we overexpressed OTUD3-Myc and KPTN-Flag in HEK-293T cells and performed immunoprecipitation experiments, which showed a clear interaction between the two proteins ( xref )."
38288086
sparser
"To test this hypothesis, we transfected KPTN shRNA into PTEN-KO HeLa cells exogenously expressing OTUD3-Myc, observing whether OTUD3 could still inhibit the mTORC1 signaling pathway in the absence of both PTEN and KPTN."
38288086
sparser
"Thus, to explore this issue we transiently transfected wild-type HeLa cells with OTUD3-Myc and catalytically inactive OTUD3C76A-Myc, using HeLa cells transfected with an empty vector as a control."
38288086
sparser
"In subsequent experiments, we exogenously expressed OTUD3-Myc in PTEN-knockout HeLa cells and subjected these cells to time-gradient amino acid starvation or amino acid starvation followed by stimulation."
38288086
sparser
"Additionally, we transfected OTUD3-Myc as an experimental group in HeLa cells with endogenous OTUD3 knocked out or HeLa cells with endogenous KPTN knocked out."
38288086
sparser
"We reintroduced exogenous OTUD3-Myc and catalytically inactive OTUD3C76A-Myc into these cells and subjected them to a time gradient of amino acid starvation or amino acid stimulation after starvation."
38288086
sparser
"We performed co-immunoprecipitation with KPTN-Flag using OTUD3-Myc and OTUD3C76A-Myc and found that the enzymatically inactive OTUD3C76A retains its ability to interact with KPTN-Flag ( xref )."
38288086
sparser
"Overexpressed KPTN-Flag and Ub-HA HEK-293T cells, along with varying levels of OTUD3-Myc or enzymatically inactive OTUD3C76A-Myc, were established."
38288086
sparser
"Myc-OTUD3 and Flag-SMAD1-7 expressing vectors were co-transfected into HEK293T cells, and the cell lysate was subjected to co-immunoprecipitation."
40382618
sparser
"Interestingly, in wild-type HeLa cells overexpressing OTUD3-Myc, although the phosphorylation trend of S6K1 was similar, the overall phosphorylation level was significantly reduced compared to wild-type HeLa cells ( xref )."
38288086
MYC phosphorylates OTUD3.
| 1
MYC phosphorylates OTUD3. 1 / 1
| 1
sparser
"In vitro kinase assays showed that OTUD3 protein was phosphorylated by Myc-PLK1 protein that were purified from HEK-293T cells (Fig. xref )."
38351178
OTUD3 affects apoptotic process
| 16
OTUD3 activates apoptotic process.
| 10
reach
"OTUDin3 induces NSCLC cell apoptosis."
37369659
reach
"The results showed that OTUDin3 induced apoptosis in H1299 cells in a concentration-dependent manner (Fig. 2E, F)."
37369659
reach
"Consistently, OTUDin3 increased the levels of apoptosis-associated proteins, Cleaved poly (ADP-ribose) polymerase (PARP) and Cleaved Caspase-3, in a concentration-dependent manner (Fig. 2G)."
37369659
reach
"Together, the results indicated that OTUDin3 induced NSCLC cell apoptosis."
37369659
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."
31338872
reach
"Pu et al. reported that OTUD3 induced growth inhibition and apoptosis in invasive breast cancer cells through the direct deubiquitination and stabilization of p53 [37]."
39415292
reach
"MiR-32 also inhibits the expression of OTUD3 and promotes cell proliferation and motility and inhibits apoptosis in colon cancer cells (Jin et al., 2019)."
37829187
reach
"Taken together, these results demonstrated that OTUDin3 inhibited lung cancer cell growth, migration and invasion, and induced apoptosis by targeting OTUD3."
37369659
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion, and induces apoptosis by targeting OTUD3."
37369659
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)."
32571254
OTUD3 inhibits apoptotic process.
| 6
OTUD3 inhibits apoptotic process. 6 / 6
| 6
reach
"However, in lung cancer, OTUD3 promotes tumour proliferation and metastasis and inhibits apoptosis through deubiquitination of GRP78 protein and is closely related to drug resistance (163)."
36969062
reach
"Downregulation of OTUD3 reduced the binding ability of Fortilin to IRE1α, thereby activating the IRE1α pathway and inducing ER stress and neuronal apoptosis."
37107185
reach
"The deubiquitinase OTUD3 has been shown to mediate endoplasmic reticulum stress to inhibit dopaminergic neuronal apoptosis by regulating Fortilin stability [28]."
39415292
reach
"In the present study, our results demonstrated that OTUD3 knockdown-induced ER stress and cell apoptosis through the activation of the IRE1α pathway but not the PERK or ATF6α pathways."
37107185
reach
"Reversal of OTUD3 protein expression or treatment with IRE1α inhibitor STF-083010 could ameliorate IRE1α signal activation and inhibit apoptosis."
37107185
reach
"OTUD3 regulates the level of fortilin ubiquitination, affects endoplasmic reticulum stress, and inhibits dopaminergic neuronal apoptosis (Chen et al., 2023)."
37829187
OTUD3 affects Carcinogenesis
| 1 14
OTUD3 activates Carcinogenesis.
| 1 11
OTUD3 activates Carcinogenesis. 10 / 12
| 1 11
reach
"A previous study demonstrated that OTUD3 promotes lung tumorigenesis by stabilizing GRP78 [26]."
37369659
reach
"Our previous study confirmed that OTUD3 promotes lung tumorigenesis by stabilizing the substrate GRP78 [2]."
38539203
eidos
"These results suggested that OTUD3 may promote tumorigenesis in leukemia ."
34815255
reach
"These results suggested that OTUD3 may promote tumorigenesis in leukemia."
34815255
reach
"OTUD3 is a member of the OTU family that participates in the regulation of multiple physiological processes, and the aberrant expression of OTUD3 triggers tumorigenesis in esophageal cancer, breast cancer and papillary thyroid carcinoma (87,88)."
40337608
reach
"Our previous study indicated that OTUD3 promoted lung tumorigenesis through stabilizing the glucose-regulated protein 78 kDa (GRP78) [2, 17]."
38539203
reach
"OTUD3 can stabilize Bip and promote lung tumorigenesis [40], whereas it suppresses breast tumorigenesis through stabilizing the PTEN protein [42]."
37107185
reach
"Remarkably, OTUD3 promotes lung tumorigenesis by stabilizing the glucose-regulated protein 78 kDa (GRP78) [26], which is a multifunctional protein with activities far beyond its well-known role in controlling unfolded protein response and implicated in promoting tumor proliferation, metastasis and involved in drug resistance [30–36]."
37369659
reach
"OTUD3 promotes lung tumorigenesis by stabilizing GRP78 [44], while it stabilizes ACTN4 to drive hepatocellular carcinoma progression and metastasis [45]."
38351178
reach
"OTUD3 is a potential tumor suppressor in NSCLC, a deubiquitylase of GRP78, and promotes tumorigenesis of NSCLC (89)."
36727069
OTUD3 inhibits Carcinogenesis.
| 3
OTUD3 inhibits Carcinogenesis. 3 / 4
| 3
reach
"In breast cancer, OTUD3 suppresses tumorigenesis and progression by stabilizing PTEN [46]."
38351178
reach
"In addition to regulating GRP78 to promote tumorigenesis in NSCLC, OTUD3 suppressed tumorigenesis in breast, colon, liver, brain, esophageal, and cervical cancer by stabilizing PTEN, ZFP36 or p53 [23–25]."
37369659
reach
"OTUD3 can stabilize Bip and promote lung tumorigenesis [40], whereas it suppresses breast tumorigenesis through stabilizing the PTEN protein [42]."
37107185
OTUD3 affects OTUD3
| 15
OTUD3 inhibits OTUD3.
| 7
OTUD3 inhibits OTUD3. 6 / 6
| 6
reach
"To further confirm that OTUDin3 is an inhibitor of OTUD3, we first performed surface plasma resonance (SRP) assays."
37369659
reach
"This implied that OTUDin3 bound to OTUD3 with a certain specificity.Next, we performed in vitro deubiquitination assays to verify whether OTUDin3 inhibits the deubiquitinating activity of OTUD3."
37369659
reach
"The results indicated that OTUDin3 inhibited the deubiquitinating activity of OTUD3 to cleave K48- and K63- linked diUb (Fig. 1K, Supplementary Fig. 1F)."
37369659
reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
32483383
reach
"OTUDin3 enhanced degradation of the substrate GRP78 by inhibiting the deubiquitinating activity of OTUD3."
37369659
reach
"OTUDin3 downregulates GRP78 by inhibiting the deubiquitinating activity of OTUD3."
37369659
OTUD3 bound to OTUD3 inhibits OTUD3. 1 / 1
| 1
reach
"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
OTUD3 activates OTUD3.
| 4
OTUD3 activates OTUD3. 4 / 4
| 4
reach
"Taken together, these results demonstrated that OTUDin3 inhibited lung cancer cell growth, migration and invasion, and induced apoptosis by targeting OTUD3."
37369659
reach
"OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
reach
"For example, the acetyltransferase CBP promotes OTUD3 acetylation for its nuclear translocation, allowing OTUD3 to deubiquitinate and stabilize the intranuclear metabolism-associated transcription factor PPARδ thereby affecting gene expression related to glycolipid metabolism and oxidative phosphorylation (OXPHOS) (Zhou et al., 2022) (Figure 3B)."
37829187
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion, and induces apoptosis by targeting OTUD3."
37369659
OTUD3 deubiquitinates OTUD3.
| 1
OTUD3 leads to the deubiquitination of OTUD3. 1 / 1
| 1
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
OTUD3 decreases the amount of OTUD3.
| 1
OTUD3 decreases the amount of OTUD3. 1 / 1
| 1
reach
"To observe the effect of OTUD3 on cell survival, Lv-shRNA-OTUD3 was constructed to knockdown the expression of OTUD3 in SH-SY5Y cells (Figure 1A,B)."
37107185
OTUD3 deacetylates OTUD3.
| 1
OTUD3 deacetylates OTUD3. 1 / 1
| 1
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"Upon virus infection, SIRT1 was recruited to associate and co-localize with cytoplasmic OTUD3, which deacetylated OTUD3 and led to the loss of its ability to cleave MAVS Lys63-linked Ub."
32679077
OTUD3 acetylates OTUD3.
| 1
OTUD3 acetylates OTUD3. 1 / 1
| 1
reach
"In addition to the DNA virus infection, acetylation of OTU deubiquitinase 3 (OTUD3) has been verified to be critical to the RNA virus infection."
36577755
CREBBP affects OTUD3
| 6 8
CREBBP acetylates OTUD3.
| 3 4
CREBBP acetylates OTUD3. 7 / 7
| 3 4
reach
"However, without glucose (0 mM), CBP cannot acetylate OTUD3 ( Figure 6 D, lane 5 versus lane 4)."
35675826
sparser
"However, without glucose (0 mM), CBP cannot acetylate OTUD3 ( Figure 6 D, lane 5 versus lane 4)."
35675826
reach
"The acetyltransferase CBP promotes OTUD3 acetylation to its nuclear translocation, where OTUD3 regulates glycolipid metabolism and oxidative phosphorylation (OXPHOS) processes through the stabilization of the metabolism-associated factor peroxisome-proliferator-activated receptor delta (PPARδ) (Zhou et al., 2022) (Figure 2C)."
37829187
sparser
"The acetyltransferase CBP promotes OTUD3 acetylation to its nuclear translocation, where OTUD3 regulates glycolipid metabolism and oxidative phosphorylation (OXPHOS) processes through the stabilization of the metabolism-associated factor peroxisome-proliferator-activated receptor delta (PPARδ) ( xref ) ( xref )."
37829187
reach
"For example, the acetyltransferase CBP promotes OTUD3 acetylation for its nuclear translocation, allowing OTUD3 to deubiquitinate and stabilize the intranuclear metabolism-associated transcription factor PPARδ thereby affecting gene expression related to glycolipid metabolism and oxidative phosphorylation (OXPHOS) (Zhou et al., 2022) (Figure 3B)."
37829187
sparser
"For example, the acetyltransferase CBP promotes OTUD3 acetylation for its nuclear translocation, allowing OTUD3 to deubiquitinate and stabilize the intranuclear metabolism-associated transcription factor PPARδ thereby affecting gene expression related to glycolipid metabolism and oxidative phosphorylation (OXPHOS) ( xref ) ( xref )."
37829187
sparser
"More importantly, we found that glucose and fatty acids can stimulate CREB-binding protein (CBP)-dependent OTUD3 acetylation and promote its nuclear translocation, where OTUD3 regulates various genes [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
CREBBP binds OTUD3.
| 2 4
OTUD3 binds CREBBP. 6 / 6
| 2 4
sparser
"The data of that study suggested that the CREB-binding-protein-dependent OTUD3 (CBP–OTUD3) signaling pathway plays a key role in glucose and fatty acid metabolism."
36531510
sparser
"Also, increased interaction between CBP and OTUD3 was correlated with increases in glucose and fatty acid concentrations ( Figure S7 I, lanes 3–5 versus lane 2)."
35675826
sparser
"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) ( xref )."
36531510
reach
"Also, increased interaction between CBP and OTUD3 was correlated with increases in glucose and fatty acid concentrations ( Figure S7 I, lanes 3–5 versus lane 2)."
35675826
reach
"Additionally, we found that high glucose levels increase the interaction between OTUD3 and CBP."
35675826
sparser
"Additionally, we found that high glucose levels increase the interaction between OTUD3 and CBP."
35675826
CREBBP increases the amount of OTUD3.
| 1
CREBBP increases the amount of OTUD3. 1 / 1
| 1
reach
"We found that the acetylation levels of OTUD3 significantly increased by the ectopic expression of CBP in a dose-dependent manner ( Figure 6 D, lanes 2–4 versus lane 1)."
35675826
IREB2 affects OTUD3
3 | 2 8
OTUD3 binds IREB2. 10 / 13
3 | 2 8
sparser
"Co-IP further confirmed the interaction between OTUD3 and IRP2 (Fig.  xref C)."
39415292
sparser
"These findings position the OTUD3-IRP2 axis as a promising therapeutic target for preventing iron-mediated neurodegeneration in PD, offering a novel approach to modify disease progression by maintaining proper iron homeostasis."
41204197
reach
"Co-IP further confirmed the interaction between OTUD3 and IRP2 (Fig. 2C)."
39415292
reach
"Subsequently, the interaction between OTUD3 and IRP2 was determined."
35490179
sparser
"OTUD3, a deubiquitinating enzyme of IRP2, interacts with IRP2 in the cytoplasm, and deubiquitinates and stabilizes the IRP2 protein in an iron-independent manner."
39415292
biogrid
No evidence text available
35490179
sparser
"The functional significance of the OTUD3-IRP2 axis is particularly evident in pathological states."
41437362
sparser
"Subsequently, the interaction between OTUD3 and IRP2 was determined."
35490179
sparser
"In line with this, hou et al. further broader significance of the OTUD3-IRP2 axis in PD iron homeostasis (Hou et al. xref )."
41204197
biogrid
No evidence text available
35490179
YY1 affects OTUD3
| 7 5
YY1 binds OTUD3.
| 6 5
OTUD3 binds YY1. 10 / 11
| 6 5
sparser
"Importantly, interactions between endogenous YY1 and OTUD3 were observed in SW480, LoVo and DLD1 cells (Fig. xref and Supplementary Fig. xref )."
38351178
sparser
"OTUD3 directly binds to and deubiquitinates YY1, preventing its proteasomal degradation."
41437362
sparser
"Notably, the OTUD3-YY1 axis provides a compelling link between inflammatory signals and CRC progression, consistent with YY1 upregulation in inflammation-associated cancers [ xref ]."
41437362
reach
"Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1."
38351178
reach
"Importantly, interactions between endogenous YY1 and OTUD3 were observed in SW480, LoVo and DLD1 cells (Fig. 1C and Supplementary Fig. S1B)."
38351178
reach
"Furthermore, in vitro pull-down assays with purified recombinant proteins showed that YY1 directly bound GST-OTUD3, not GST control (Fig. 1D)."
38351178
reach
"An in-situ proximity ligation assay (PLA) was performed to identify the interactions between endogenous YY1 and OTUD3 in CRC cells."
38351178
reach
"Then, the immunoprecipitation assays confirmed that up-regulated PLK1 promoted the physical binding between OTUD3 and YY1, but failed to promote the binding between OTUD3 mutation (S326A) and YY1 (Fig. 5L–N and Supplementary Fig. S5A, B)."
38351178
sparser
"We found that OTUD3 directly interacts with YY1."
38351178
sparser
"OTUD3 interacts with YY1."
38351178
YY1 activates OTUD3.
| 1
YY1 activates OTUD3. 1 / 1
| 1
reach
"To determine whether OTUD3 promotes tumor progression by regulating YY1, we restored the expression of YY1 in endogenous OTUD3 depletion CRC cells or knocked down endogenous YY1 in OTUD3-overexpressing CRC cells."
38351178
STUB1 affects OTUD3
2 | 1 5 2 2
STUB1 binds OTUD3.
2 | 2 1
OTUD3 binds STUB1. 5 / 5
2 | 2 1
biogrid
No evidence text available
32483383
reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
32483383
biogrid
No evidence text available
32483383
reach
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [98]."
38841185
sparser
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [ xref ]."
38841185
STUB1 ubiquitinates OTUD3.
| 2 1
STUB1 ubiquitinates OTUD3. 3 / 3
| 2 1
sparser
"The ubiquitin ligase CHIP ubiquitinates OTUD3 to degrade it, and inhibition of the OTUD3-GRP78 signaling axis reduces tumor metastasis in lung cancer ( xref )."
37829187
reach
"The ubiquitin ligase CHIP ubiquitinates OTUD3 to degrade it, and inhibition of the OTUD3-GRP78 signaling axis reduces tumor metastasis in lung cancer (Zhang et al., 2020b)."
37829187
reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
32483383
STUB1 inhibits OTUD3.
| 1 1
STUB1 bound to OTUD3 inhibits OTUD3. 1 / 1
| 1
reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
32483383
STUB1 inhibits OTUD3. 1 / 1
| 1
eidos
"CHIP interacts with , polyubiquitylates OTUD3 and promotes OTUD3 degradation ."
32483383
STUB1 increases the amount of OTUD3.
| 2
STUB1 increases the amount of OTUD3. 1 / 2
| 2
isi
"Moreover, the expression of CHIP is low in human lung cancer tissues and inversely correlates with OTUD3 expression and GRP78 expression."
32483383
OTUD3 affects KPTN
1 | 11
OTUD3 deubiquitinates KPTN.
| 4
OTUD3 deubiquitinates KPTN. 4 / 4
| 4
reach
"Results revealed that exogenous KPTN was indeed ubiquitinated, and the presence of OTUD3 reduced the level of KPTN ubiquitination in a manner directly proportional to OTUD3 protein levels."
38288086
reach
"We found that OTUD3 significantly deubiquitinates KPTN, effectively removing polyubiquitin chains on the lysine 49 residue."
38288086
reach
"OTUD3’s knockout leads to abnormal mTORC1 pathway activation, resulting in Warburg effect induction and increased synthesis-related metabolism.While our study elucidates how OTUD3 regulates the mTORC1 pathway by deubiquitinating KPTN and influencing the recruitment of the KICSTOR complex to GATOR1, many aspects remain to be fully explored."
38288086
reach
"3.2 OTUD3 promoted the deubiquitination of KPTN but did not affect its protein levels."
38288086
OTUD3 binds KPTN.
1 | 3
OTUD3 binds KPTN. 4 / 4
1 | 3
reach
"Our experiments indicated that the OTU domain plays a pivotal role in the interaction between OTUD3 and KPTN (Figures 1D, E)."
38288086
biogrid
No evidence text available
33961781
reach
"Through this method, we found that there is a potential interaction between the deubiquitinating enzyme OTUD3 and KPTN, which is one of the components of the KICSTOR protein complex, an important regulatory factor in the mTORC1 signaling pathway.Researchers have identified gene mutations in the breast cancer cell lines involving OTUD3, leading to loss of protein function and accelerating the migration and metastasis of cancer cells."
38288086
reach
"Thus, these results validated the interaction between OTUD3 and KPTN."
38288086
OTUD3 activates KPTN.
| 2
OTUD3 activates KPTN. 2 / 2
| 2
reach
"Then we examined whether OTUD3’s deubiquitination prevents KPTN degradation or affects its functionality."
38288086
reach
"3.5 OTUD3 mediated the lysosomal localization of GATOR1 and this process requires the participation of KPTN."
38288086
OTUD3 ubiquitinates KPTN.
| 1
OTUD3 ubiquitinates KPTN. 1 / 1
| 1
reach
"OTUD3 suppresses the mTORC1 signaling by deubiquitinating KPTN."
38288086
OTUD3 decreases the amount of KPTN.
| 1
OTUD3 decreases the amount of KPTN. 1 / 1
| 1
reach
"Results revealed that exogenous KPTN was indeed ubiquitinated, and the presence of OTUD3 reduced the level of KPTN ubiquitination in a manner directly proportional to OTUD3 protein levels."
38288086
OTUD3 affects PLK1
| 3 8
OTUD3 binds PLK1. 10 / 10
| 2 8
sparser
"These results indicate that OTUD3 interacted with PLK1, and PLK1‐T2 (36–305) is the sequence of PLK1 that binds to OTUD3."
40462502
sparser
"We next used co‐immunoprecipitation and western blot methods to analyse the specific fragments of OTUD3 and PLK1 that bind to each other."
40462502
sparser
"To explore the regions responsible for the interactions between OTUD3 and PLK1, we generated a set of deletion mutants of PLK1."
38351178
sparser
"In previous studies, PLK1 was shown to be involved in ferroptosis in tumour cells and played a key role in promoting tumour cell growth. xref We predicted the binding of OTUD3 and PLK1 proteins using molecular docking techniques."
40462502
sparser
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
sparser
"Binding of OTUD3 to PLK1."
40462502
reach
"In vitro pull-down assays with purified recombinant proteins showed that Myc-PLK1 directly bound GST-OTUD3, instead of GST control (Fig. 5G)."
38351178
reach
"To explore the regions responsible for the interactions between OTUD3 and PLK1, we generated a set of deletion mutants of PLK1."
38351178
sparser
"Dysregulation of its activity not only directly leads to chromosomal segregation errors and micronucleus formation but may also exacerbate oncogenic risk by interfering with DNA damage repair pathways, making it a highly promising molecular target in cancer therapy. xref , xref , xref Co‐immunoprecipitation and mass spectrometry showed that OTUD3 interacted with PLK1 and then truncated PLK1 into three parts."
40462502
sparser
"Ectopically expressed HA-tagged OTUD3 also interacted with Myc-tagged PLK1 in HEK-293T cells, and vice versa (Fig. xref and Supplementary Fig. xref )."
38351178
PLK1 binds OTUD3 and PBD domain. 1 / 1
| 1
reach
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
CGAS affects OTUD3
5 | 6
CGAS binds OTUD3. 9 / 9
5 | 4
reach
"At the same time, the same amount of HA-OTUD3 WT and HA-OTUD3 CA were captured in corresponding pull-down samples, meaning that more FLAG-cGAS was not pulled down due to the interaction between cGAS a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"41 OTUD3-DNA interaction can lead OTUD3 to the cytosolic DNA complex and increase the association between cGAS and OTUD3, which is in agreement with the results of cGAS proximity labeling."
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
biogrid
No evidence text available
36966392
reach
"In addition, OTUD3 C76A catalytic mutation (as FLAG-OTUD3 CA) does not obviously affect the interaction between HA-cGAS and FLAG-OTUD3 ( Figure S3 C)."
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"This result could partially explain the enhanced association between OTUD3 and cGAS in cells under DNA activation ( Figures 3 B and 3C), and also supports that OTUD3 can be recruited to cGAS-DNA compl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
OTUD3 binds CGAS and Lys279. 1 / 1
| 1
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"OTUD3 binds cGAS and targets the Lys279 site for deubiquitination of k48- and k27-linked ubiquitination, thereby enhancing cGAS protein stability and DNA binding capacity (Cai et al., 2022)."
37829187
OTUD3-C76S binds CGAS. 1 / 1
| 1
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"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
OTUD3 affects Ubiquitin
| 5 3
OTUD3 binds Ubiquitin.
| 3 3
OTUD3 binds Ubiquitin. 6 / 8
| 3 3
sparser
"Then, we performed in vitro OTUD3-Ub binding assays with OTUDin3 to verify whether OTUDin3 interfered with OTUD3 binding to Ub as designed."
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"The results showed that OTUDin3 inhibited the binding of OTUD3 to Ub (Fig. xref )."
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"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
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"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
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"Then, we performed in vitro OTUD3-Ub binding assays with OTUDin3 to verify whether OTUDin3 interfered with OTUD3 binding to Ub as designed."
37369659
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"The results showed that OTUDin3 inhibited the binding of OTUD3 to Ub (Fig. 1L)."
37369659
OTUD3 activates Ubiquitin.
| 2
OTUD3 activates Ubiquitin. 2 / 2
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"OTUD3 enhances the stability of YY1 by cleaving ubiquitin molecules from YY1 at K332, K339 and K409 residues."
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"OTUD3 loss of function increases the Ub-dependent degradation of PTEN and enhances PI3K/AKT signaling in breast cancer cells ( Yuan et al., 2015 )."
35675826
OTUD3 affects RIGI
| 8 2
OTUD3 inhibits RIGI.
| 5 1
OTUD3 inhibits RIGI. 6 / 6
| 5 1
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"These results suggest that OTUD3 deubiquitinates K63-linked polyubiquitination of RIG-I and MDA5.Overexpression of OTUD3 in HEK293T cells inhibited the oligomerization of RIG-I or MDA5 when these were[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
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"Coinciding with these observations, the overexpression of OTUD3 markedly inhibited the self-association of RIG-I and MDA5, as well as the association of MAVS with RIG-I or MDA5 ( Figures S4 E–S4H)."
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"Taken together, these data suggest that OTUD3 inhibits RNF135-induced RIG-I and TRIM65-induced MDA5 activation."
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"In contrast, knockdown OTUD3 in HEK293T by CRISPR-Cas9 cells enhanced the self-association of RIG-I and MDA5, and the association of MAVS with RIG-I or RIG-I or MDA5 ( Figures S4 I–S4L)."
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"In vitro pull-down experiments showed that overexpression of OTUD3 inhibited the binding of RIG-I to 5′-ppp-dsRNA ( Figure S4 M), as well as of MDA5 to poly(I:C)-HMW ( Figure S4 N)."
35675783
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"These findings suggest that OTUD3 inhibits the oligomerization of RIG-I and MDA5 and prevents the binding of viral RNA to RIG-I and MDA5.To determine the functional role of OTUD3 in the activation of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 binds RIGI.
| 3 1
OTUD3 binds RIGI. 3 / 3
| 2 1
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"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
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"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
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"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
OTUD3 binds RIGI and K63. 1 / 1
| 1
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"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
OTUD3 affects FlaG
| 10
OTUD3 binds FlaG. 10 / 10
| 10
sparser
"In addition, OTUD3 C76A catalytic mutation (as FLAG-OTUD3 CA) does not obviously affect the interaction between HA-cGAS and FLAG-OTUD3 ( Figure S3 C)."
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sparser
"Moreover, under HT-DNA activation, association of endogenous cGAS with FLAG-OTUD3 or endogenous OTUD3 was enhanced, probably due to the higher expression of endogenous cGAS induced by DNA activation ([MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"By using 90-bp dsDNA in DNA shift assay ( Figures 6 C and 6D), we further established that the Kd (equilibrium dissociation constant) of 90-bp dsDNA binding to OTUD3 is about 0.5 μM. To examine whethe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"19 According to the study showing that OTUD3 associates with mitochondrial antiviral-signaling protein (MAVS) to suppress anti-RNA viral immune response, 17 we also performed coIP experiments using F[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"29 , 30 , 31 To examine whether OTUD3 affects cGAS enzymatic activity, FLAG-cGAS was purified from 293T shOTUD3#1cells and treated with FLAG-OTUD3 WT or CA in vitro , followed by cGAS enzymatic assay."
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"From in vitro assays using FLAG-OTUD3 WT/CA purified from 293T cells and FLAG-cGAS bearing polyUb purified from 293T shOTUD3#1 cells (either in native condition or denaturing condition), it is clear t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"As shown in Figure 1 I, FLAG-OTUD3 and GFP-cGAS are colocalized in cytosolic GFP-cGAS-DNA complex under DNA activation in HeLa cells."
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"Furthermore, in THP-1 FLAG-OTUD3 cells, besides some low overlap of FLAG-OTUD3 and endogenous cGAS in resting conditions, concentrated FLAG-OTUD3 resides in endogenous cGAS-DNA complex not only under [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"As shown in Figure 6 E, FLAG-OTUD3 indeed pulled down 500-bp DNA the same as FLAG-cGAS, while GFP-FLAG could not."
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"To investigate whether OTUD3 interacts with cGAS, we carried out coIP from cells using FLAG-OTUD3 together with hemagglutinin (HA)-cGAS, and found HA-cGAS in FLAG-OTUD3 IP sample but not in control im[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
Rolapitant affects OTUD3
| 9
Rolapitant inhibits OTUD3.
| 8
Rolapitant inhibits OTUD3. 8 / 8
| 8
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"But we found that when Rolapitant was added to lung cancer cells, Rolapitant inhibits the deubiquitinating activity of OTUD3, thereby promoting GRP78 ubiquitination and resulting in its degradation."
38539203
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"Based on our data, we propose that Rolapitant directly inhibit the deubiquitinating activity of OTUD3 through binding to OTUD3 to cause the downregulation of GRP78 protein levels."
38539203
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"The results indicated that Rolapitant inhibited the deubiquitinating activity of OTUD3 to cleave K48- linked di-Ub (Fig. 3E)."
38539203
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"Rolapitant inhibits lung cancer cell growth by targeting OTUD3."
38539203
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"These results implied that Rolapitant suppresses the proliferation of lung cancer cells via OTUD3."
38539203
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"Rolapitant inhibits the deubiquitinating activity of OTUD3."
38539203
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"Next, we performed in vitro deubiquitination assays to further verify whether Rolapitant inhibits the deubiquitinating activity of OTUD3 in vitro."
38539203
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"Rolapitant inhibited the proliferation of lung cancer cells by inhibiting deubiquitinating activity of OTUD3."
38539203
Rolapitant binds OTUD3.
| 1
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"Moreover, MST (microscale thermophoresis) assays shown that OTUD3 could directly bind to Rolapitant in vitro, but not bind well to Estradiol Cypionate (Fig. 1H)."
38539203
OTUD3 affects mTORC1
| 9
OTUD3 inhibits mTORC1.
| 8
OTUD3 inhibits mTORC1. 8 / 8
| 8
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"These findings partially confirm the essential role of the KPTN protein in OTUD3’s ability to downregulate the mTORC1 signaling pathway in cells."
38288086
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"3.6 OTUD3 suppressed proliferation and growth of HeLa by downregulating the mTORC1."
38288086
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"Under various amino acid starvation or stimulation conditions, overexpressing OTUD3 reduces mTORC1 signaling activation, while knocking out OTUD3 further enhances it."
38288086
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"3.3 OTUD3 downregulated mTORC1 signaling pathway on account of its enzymatic deubiquitinase activity."
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"To test this hypothesis, we transfected KPTN shRNA into PTEN-KO HeLa cells exogenously expressing OTUD3-Myc, observing whether OTUD3 could still inhibit the mTORC1 signaling pathway in the absence of both PTEN and KPTN."
38288086
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"The results showed that the ability of OTUD3 to inhibit the mTORC1 signaling pathway was significantly weakened under conditions of concurrent PTEN and KPTN depletion (Figure 4E)."
38288086
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"Furthermore, OTUD3’s downregulation of the mTORC1 pathway requires the presence of its substrate, KPTN."
38288086
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"This suggests that OTUD3C76A, lacking deubiquitinase activity, cannot reverse the upregulation of the mTORC1 signaling pathway caused by the knockout of endogenous OTUD3.In this section of the study, through a series of experiments involving amino acid starvation and stimulation in HeLa cells, we demonstrated that OTUD3 can downregulate the mTORC1 signaling pathway, and this downregulation is dependent on the enzymatic deubiquitinase activity of OTUD3."
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OTUD3 decreases the amount of mTORC1.
| 1
OTUD3 decreases the amount of mTORC1. 1 / 1
| 1
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"We started by observing a phenomenon: OTUD3 can reduce the levels of the mTORC1 signaling pathway."
38288086
OTUD3 affects cell growth
| 1 8
OTUD3 inhibits cell growth.
| 8
OTUD3 inhibits cell growth. 8 / 8
| 8
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"OTUDin3 inhibits NSCLC cell growth, migration and invasion."
37369659
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"Over-expression of OTUD3 suppressed YY1 degradation and promoted CRC cell growth."
38351178
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"The results indicated that stable expression of OTUD3 inhibited HeLa cell growth, while OTUD3 knockout promoted HeLa cell growth (Figures 6B, C)."
38288086
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"Collectively, these results demonstrated that OTUDin3 inhibited NSCLC cell growth, migration and invasion."
37369659
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"OTUDin3 inhibits NSCLC cell growth, migration and invasion, and induces apoptosis by targeting OTUD3."
37369659
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"In lung cancer, OTUD3 interacts with GRP78, inhibiting cell growth and migration (Du et al., 2019)."
38288086
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"However, we observed that OTUDin3 still inhibited cell growth after OTUD3 knockdown."
37369659
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"Taken together, these results demonstrated that OTUDin3 inhibited lung cancer cell growth, migration and invasion, and induced apoptosis by targeting OTUD3."
37369659
OTUD3 activates cell growth.
| 1
OTUD3 activates cell growth. 1 / 1
| 1
eidos
"Compared with the control cells , OTUD3 depletion suppressed cell growth and migration ( Fig. 4a , d and supplementary Fig. 4a , c ) ."
31266968
OTUD3 affects ERN1
| 1 6 2
OTUD3 inhibits ERN1.
| 1 5
OTUD3 inhibits ERN1. 6 / 6
| 1 5
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"These results showed that OTUD3 knockdown-induced ER stress activated the IRE1α pathway."
37107185
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"OTUD3 knockdown increased the activation of IRE1α and the expression of XBP1s."
37107185
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"To explore the underlying mechanism by which OTUD3 knockdown activated the IRE1α pathway, we performed co-immunoprecipitation (Co-IP) to detect protein interactions."
37107185
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"Downregulation of OTUD3 reduced the binding ability of Fortilin to IRE1α, thereby activating the IRE1α pathway and inducing ER stress and neuronal apoptosis."
37107185
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"Taken together, we revealed that OTUD3 knockout-induced injury of dopaminergic neurons might be caused by activating IRE1alpha signaling in ER stress."
37107185
eidos
"OTUD3 knockdown resulted in a decrease in the interaction ability of IRE1alpha with Fortilin and finally enhanced the activity of IRE1alpha ."
37107185
OTUD3 binds ERN1.
| 2
OTUD3 binds ERN1. 2 / 2
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"Our findings indicated that OTUD3 did not directly interact with IRE1α, as endogenous OTUD3 was not immunoprecipitated by IRE1α antibody in shRNA-NC and OTUD3 knockdown cells ( xref A)."
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sparser
"The results showed that there was no interaction between IRE1α and OTUD3."
37107185
OTUD3 activates ERN1.
| 1
OTUD3 activates ERN1. 1 / 1
| 1
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"OTUD3 knockdown resulted in a decrease in the interaction ability of IRE1alpha with Fortilin and finally enhanced the activity of IRE1alpha."
37107185
Ubiquitin affects OTUD3
| 3 3
OTUD3 binds Ubiquitin. 6 / 8
| 3 3
sparser
"Then, we performed in vitro OTUD3-Ub binding assays with OTUDin3 to verify whether OTUDin3 interfered with OTUD3 binding to Ub as designed."
37369659
sparser
"The results showed that OTUDin3 inhibited the binding of OTUD3 to Ub (Fig. xref )."
37369659
sparser
"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
reach
"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
reach
"Then, we performed in vitro OTUD3-Ub binding assays with OTUDin3 to verify whether OTUDin3 interfered with OTUD3 binding to Ub as designed."
37369659
reach
"The results showed that OTUDin3 inhibited the binding of OTUD3 to Ub (Fig. 1L)."
37369659
OTUD3 affects immune response
| 8
OTUD3 inhibits immune response.
| 5
OTUD3 inhibits immune response. 5 / 5
| 5
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"OTUD3 specifically hydrolyzes Lys63-linked Ub of MAVS and thus represses innate antiviral immune response both in vitro and in vivo ."
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"Here, we show that OTUD3 inhibits the innate antiviral immune response to RNA viruses but promotes the innate antiviral immune response to DNA viruses, highlighting the complexity of innate antiviral [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, OTUD3 represses type I interferon expression and virus defense of cells dependent on its DUB activity.To investigate the role of OTUD3 in innate antiviral immunity in vivo , we generated Otu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"19 According to the study showing that OTUD3 associates with mitochondrial antiviral-signaling protein (MAVS) to suppress anti-RNA viral immune response, 17 we also performed coIP experiments using FL[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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reach
"This regulation of OTUD3 prevents innate antiviral immunity from unwanted auto- or extra-activation and meanwhile enables the efficient immune response against virus."
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OTUD3 activates immune response.
| 3
OTUD3 activates immune response. 3 / 3
| 3
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"These findings suggest that otud3 also promotes DNA virus-triggered antiviral immune response in zebrafish.The opposing effects on RNA virus- and DNA virus-triggered antiviral immune response exhibite[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
reach
"This regulation of OTUD3 prevents innate antiviral immunity from unwanted auto- or extra-activation and meanwhile enables the efficient immune response against virus."
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reach
"Here, we show that OTUD3 inhibits the innate antiviral immune response to RNA viruses but promotes the innate antiviral immune response to DNA viruses, highlighting the complexity of innate antiviral [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects NFE2L2
| 5 3
OTUD3 binds NFE2L2. 7 / 7
| 4 3
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"The interaction of NRF2 and OTUD3 was further confirmed by Co-IP, and it was shown that NRF2 could form a complex with OTUD3, which was abolished by the knockdown of BUB1b (Fig. 5D)."
39043653
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"Thus, the interaction of OTUD3 and NRF2 was BUB1b dependent."
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"We also explored the impact of the kinase activity of BUB1b on the recruitment of OTUD3 and NRF2."
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"We found that the recruitment of OTUD3 to NRF2 by BUB1b stabilized the protein level of NRF2 and enhanced resistance to ferroptosis, which conferred chemoresistance to LUAD."
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sparser
"Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy."
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"The interaction of NRF2 and OTUD3 was further confirmed by Co-IP, and it was shown that NRF2 could form a complex with OTUD3, which was abolished by the knockdown of BUB1b (Fig. xref )."
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sparser
"Thus, the interaction of OTUD3 and NRF2 was BUB1b dependent."
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BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
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"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
OTUD3 affects IL6
| 8
OTUD3 increases the amount of IL6.
| 5
OTUD3 increases the amount of IL6. 4 / 4
| 4
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"Overexpression of OTUD3 in THP-1 cells promoted HSV-1-induced IFNβ , ISG56 , CXCl10 , and IL6 expression steadily with the increase in infection time ( Figure 5 A ), in contrast to its impact on RNA v[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
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"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Moreover, knockdown of OTUD3 also suppressed ISD45-induced IFNβ , ISG56 , CXCl10 , and IL6 expression ( Figure 5 C)."
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"Additionally, knockdown of OTUD3 in HFF cells enhanced SeV- and EMCV-induced IFNB1 and IL6 expression, whereas the ectopic expression of OTUD3 suppressed the SeV- and EMCV-induced IFNB1 and IL6 expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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OTUD3-C76A increases the amount of IL6. 1 / 1
| 1
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"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 inhibits IL6.
| 1
OTUD3 inhibits IL6. 1 / 1
| 1
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"IL-6, Tnf-a, IL-1b, and Nos2, which are critical NF-kB target genes activated by MAVS aggregation, are consistently and efficiently induced by SeV in OTUD3-deficient macrophages (29)."
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OTUD3 decreases the amount of IL6.
| 1
OTUD3 decreases the amount of IL6. 1 / 1
| 1
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"Additionally, knockdown of OTUD3 in HFF cells enhanced SeV- and EMCV-induced IFNB1 and IL6 expression, whereas the ectopic expression of OTUD3 suppressed the SeV- and EMCV-induced IFNB1 and IL6 expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 activates IL6.
| 1
OTUD3 activates IL6. 1 / 1
| 1
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"Il-6 , Tnf-α , Il-1β , and Nos2 , critical NF-κB target genes activated by MAVS aggregation, were consistently and more efficiently induced by SeV in Otud3 -deficient macrophages ( Figure 4 H)."
32679077
OTUD3 affects IFNB1
| 8
OTUD3 increases the amount of IFNB1.
| 3
OTUD3 increases the amount of IFNB1. 2 / 2
| 2
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"Additionally, knockdown of OTUD3 in HFF cells enhanced SeV- and EMCV-induced IFNB1 and IL6 expression, whereas the ectopic expression of OTUD3 suppressed the SeV- and EMCV-induced IFNB1 and IL6 expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3-C76A increases the amount of IFNB1. 1 / 1
| 1
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 inhibits IFNB1.
| 2
OTUD3 inhibits IFNB1. 2 / 2
| 2
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"When infected with stomatitis virus (VSV), we found that knockdown of OTUD3 potentiated the expression of VSV-induced Ifnb1 in macrophages ( Figure 1 H)."
32679077
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"In contrast, knockdown OTUD3 enhanced the IFN-β luciferase reporter activity ( Figures S5 J and S5K)."
35675783
OTUD3 activates IFNB1.
| 2
OTUD3 activates IFNB1. 2 / 2
| 2
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"Additionally, we confirmed that the enhancement of OTUD3 on cGAS/STING-induced IFN-β promoter luciferase reporter activity depended on its enzyme activity ( Figure S10 F)."
35675783
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"OTUD3 depletion by shRNA obviously potentiated the SeV-induced activity of the Ifnb1 promoter and the positive regulatory domain (PRD) I–III reporter, which contained an IRF3-binding site ( Figures S1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 decreases the amount of IFNB1.
| 1
OTUD3 decreases the amount of IFNB1. 1 / 1
| 1
reach
"Additionally, knockdown of OTUD3 in HFF cells enhanced SeV- and EMCV-induced IFNB1 and IL6 expression, whereas the ectopic expression of OTUD3 suppressed the SeV- and EMCV-induced IFNB1 and IL6 expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects GST
| 8
OTUD3 binds GST. 8 / 8
| 8
sparser
"In order to observe DNA response to the reaction, less GST-OTUD3 and less reaction time were applied compared with experiments in Figure 4 F (details in STAR Methods )."
36966392
sparser
"FLAG-cGAS bearing polyUb was purified from 293T shOTUD3#1 cells by denaturing IP and then treated with GST-OTUD3 in the absence or presence of HT-DNA in vitro ."
36966392
sparser
"Furthermore, in vitro pull-down assays with purified recombinant proteins showed that YY1 directly bound GST-OTUD3, not GST control (Fig. xref )."
38351178
sparser
"The results show that GST-OTUD3 removes WT polyUb on cGAS noticeably, and has specific deubiquitination activity toward K11-, K27-, and K48-linked polyUb on cGAS ( Figure 4 F)."
36966392
sparser
"24 To see whether OTUD3 could remove this specific modification, we generated cGAS bearing K27-linked polyUb catalyzed by RNF185 in vitro according to Wang et al. 24 ( Figure S4 A) and then treated it[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
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."
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"18 , 23 After 293T shOTUD3#1 cells were transfected with FLAG-cGAS together with Myc-Ub WT or mutants, FLAG-cGAS bearing polyUb with various chain linkages was purified from cells and then treated wit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"In vitro pull-down assays with purified recombinant proteins showed that Myc-PLK1 directly bound GST-OTUD3, instead of GST control (Fig. xref )."
38351178
NFE2L2 affects OTUD3
| 5 3
OTUD3 binds NFE2L2. 7 / 7
| 4 3
reach
"The interaction of NRF2 and OTUD3 was further confirmed by Co-IP, and it was shown that NRF2 could form a complex with OTUD3, which was abolished by the knockdown of BUB1b (Fig. 5D)."
39043653
reach
"Thus, the interaction of OTUD3 and NRF2 was BUB1b dependent."
39043653
reach
"We also explored the impact of the kinase activity of BUB1b on the recruitment of OTUD3 and NRF2."
39043653
reach
"We found that the recruitment of OTUD3 to NRF2 by BUB1b stabilized the protein level of NRF2 and enhanced resistance to ferroptosis, which conferred chemoresistance to LUAD."
39043653
sparser
"Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy."
39043653
sparser
"The interaction of NRF2 and OTUD3 was further confirmed by Co-IP, and it was shown that NRF2 could form a complex with OTUD3, which was abolished by the knockdown of BUB1b (Fig. xref )."
39043653
sparser
"Thus, the interaction of OTUD3 and NRF2 was BUB1b dependent."
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BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
reach
"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
GST affects OTUD3
| 8
OTUD3 binds GST. 8 / 8
| 8
sparser
"In order to observe DNA response to the reaction, less GST-OTUD3 and less reaction time were applied compared with experiments in Figure 4 F (details in STAR Methods )."
36966392
sparser
"FLAG-cGAS bearing polyUb was purified from 293T shOTUD3#1 cells by denaturing IP and then treated with GST-OTUD3 in the absence or presence of HT-DNA in vitro ."
36966392
sparser
"Furthermore, in vitro pull-down assays with purified recombinant proteins showed that YY1 directly bound GST-OTUD3, not GST control (Fig. xref )."
38351178
sparser
"The results show that GST-OTUD3 removes WT polyUb on cGAS noticeably, and has specific deubiquitination activity toward K11-, K27-, and K48-linked polyUb on cGAS ( Figure 4 F)."
36966392
sparser
"24 To see whether OTUD3 could remove this specific modification, we generated cGAS bearing K27-linked polyUb catalyzed by RNF185 in vitro according to Wang et al. 24 ( Figure S4 A) and then treated it[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
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."
31266968
sparser
"18 , 23 After 293T shOTUD3#1 cells were transfected with FLAG-cGAS together with Myc-Ub WT or mutants, FLAG-cGAS bearing polyUb with various chain linkages was purified from cells and then treated wit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"In vitro pull-down assays with purified recombinant proteins showed that Myc-PLK1 directly bound GST-OTUD3, instead of GST control (Fig. xref )."
38351178
CGAS affects OTUD3
| 7
OTUD3 binds cGAS. 7 / 7
| 7
sparser
"At the same time, the same amount of HA-OTUD3 WT and HA-OTUD3 CA were captured in corresponding pull-down samples, meaning that more FLAG-cGAS was not pulled down due to the interaction between cGAS a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"To investigate whether OTUD3 interacts with cGAS, we carried out coIP from cells using FLAG-OTUD3 together with hemagglutinin (HA)-cGAS, and found HA-cGAS in FLAG-OTUD3 IP sample but not in control im[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"Collectively, through its context-dependent regulation of pivotal signaling hubs—MAVS, STING, and cGAS—OTUD3 functions as a master integrator."
41437362
sparser
"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
sparser
"Because OTUD3 interacts with cGAS and its enzyme activity is required for regulating antiviral signaling, we investigated whether OTUD3 eliminated polyubiquitin chains from cGAS."
35675783
sparser
"We also demonstrate that OTUD3 can bind with DNA directly, not only leading OTUD3 to the cytosolic DNA complex but also increasing the association of cGAS with OTUD3, which indicates that OTUD3 has a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"17 Taken together, our results demonstrate that both OTUD3 WT and C76S catalytic mutant associate with cGAS."
36966392
SIRT1 affects OTUD3
| 4 3
SIRT1 inhibits OTUD3.
| 2 1
SIRT1 inhibits OTUD3. 3 / 3
| 2 1
reach
"Further, upon SeV infection, the Silent information regulator factor 2-related enzyme 1 (Sirt-1) deacetylates (K129) and inactivates OTUD3 and thereby prevents the K63-deubiquitinylation of MAVS [ 19 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34016513
reach
"In response to a viral infection, acetylated Lys129 is deacylated and eliminated by SIRT1, which rapidly inactivates OTUD3, inducing innate antiviral immunity by upregulating the viral activation of MAVS and inducing type 1 IFN (222)."
35795579
sparser
"In response to a viral infection, acetylated Lys129 is deacylated and eliminated by SIRT1, which rapidly inactivates OTUD3, inducing innate antiviral immunity by upregulating the viral activation of MAVS and inducing type 1 IFN ( xref )."
35795579
SIRT1 binds OTUD3.
| 1 2
OTUD3 binds SIRT1. 3 / 3
| 1 2
sparser
"Among the seven sirtuins (SIRT1–7) we have tested, co-expressed OTUD3 associated strongly with SIRT1 and weakly with SIRT7 ( Figure 6 C)."
32679077
sparser
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
reach
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
SIRT1 deacetylates OTUD3.
| 1
SIRT1 deacetylates OTUD3. 1 / 1
| 1
reach
"In response to viral infection, OTUD3 was deacetylated by SIRT1 and completely lost this activity, which allowed TRIM31 binding, Lys63-linked ubiquitination, and propagation of MAVS.Addition or remova[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 affects cGAS
| 7
OTUD3 binds cGAS. 7 / 7
| 7
sparser
"At the same time, the same amount of HA-OTUD3 WT and HA-OTUD3 CA were captured in corresponding pull-down samples, meaning that more FLAG-cGAS was not pulled down due to the interaction between cGAS a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"To investigate whether OTUD3 interacts with cGAS, we carried out coIP from cells using FLAG-OTUD3 together with hemagglutinin (HA)-cGAS, and found HA-cGAS in FLAG-OTUD3 IP sample but not in control im[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"Collectively, through its context-dependent regulation of pivotal signaling hubs—MAVS, STING, and cGAS—OTUD3 functions as a master integrator."
41437362
sparser
"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
sparser
"Because OTUD3 interacts with cGAS and its enzyme activity is required for regulating antiviral signaling, we investigated whether OTUD3 eliminated polyubiquitin chains from cGAS."
35675783
sparser
"We also demonstrate that OTUD3 can bind with DNA directly, not only leading OTUD3 to the cytosolic DNA complex but also increasing the association of cGAS with OTUD3, which indicates that OTUD3 has a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
sparser
"17 Taken together, our results demonstrate that both OTUD3 WT and C76S catalytic mutant associate with cGAS."
36966392
OTUD3 affects TOP2A
| 5 2
OTUD3 binds TOP2A.
| 2 2
OTUD3 binds TOP2A. 4 / 4
| 2 2
sparser
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay ( xref lane 6)."
26657567
reach
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay (XREF_FIG lane 6)."
26657567
reach
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A."
26657567
sparser
"This association of OTUD3 and TOP2A was confirmed in MEFs and HCT116 cells ( xref lane 2, 4f lane 3)."
26657567
OTUD3 increases the amount of TOP2A.
| 1
Modified OTUD3 increases the amount of TOP2A. 1 / 1
| 1
reach
"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."
26657567
OTUD3 deubiquitinates TOP2A.
| 1
OTUD3 leads to the deubiquitination of TOP2A. 1 / 1
| 1
reach
"In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3."
26657567
OTUD3 activates TOP2A.
| 1
OTUD3 activates TOP2A. 1 / 1
| 1
reach
"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)."
26657567
OTUD3 affects NSCLC
| 7
OTUD3 inhibits NSCLC.
| 5
OTUD3 inhibits NSCLC. 5 / 5
| 5
reach
"OTUDin3 inhibits NSCLC growth in vivo."
37369659
reach
"Based on these findings, we concluded that OTUDin3 inhibits NSCLC by targeting the OTUD3-GRP78 signaling axis (Fig. 6)."
37369659
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion."
37369659
reach
"Collectively, these results demonstrated that OTUDin3 inhibited NSCLC cell growth, migration and invasion."
37369659
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion, and induces apoptosis by targeting OTUD3."
37369659
OTUD3 activates NSCLC.
| 2
OTUD3 activates NSCLC. 2 / 2
| 2
reach
"In addition, a study on CHIP, an E3 ubiquitin ligase for OTUD3, further confirmed that OTUD3 promoted NSCLC through an OTUD3-GRP78 signaling axis [44]."
37369659
reach
"Collectively, we identified the first small-molecule inhibitor of OTUD3, which effectively inhibited NSCLC."
37369659
OTUD3 affects Flag
| 7
OTUD3 binds Flag. 7 / 7
| 7
sparser
"Flag-OTUD3 and His-BHLHE22 vectors were co-transfected into 293 T cells to verify exogenous OTUD3 and BHLHE22 protein interaction (Fig.  xref d)."
41484895
sparser
"Flag-OTUD3 WT or Flag-OTUD3 C76A , Myc-GRP78, and HA-Ub were transfected into HEK293T cells as indicated."
37369659
sparser
"Flag-OTUD3 WT (wild-type) or Flag-OTUD3 C76A, Myc-GRP78 and HA-Ub were transfected into HEK293T cells as indicated."
38539203
sparser
"Compared with the IgG control group, 17 proteins with a difference >4‐fold in the Flag‐OTUD3 group were initially screened as interacting proteins of OTUD3."
40462502
sparser
"Additionally, we validated this interaction by reciprocal experiments, where we overexpressed KPTN-Myc and OTUD3-Flag and obtained similar results ( xref )."
38288086
sparser
"Further confirmation involved separate overexpression of KPTN-Flag and OTUD3-Flag in HEK-293T cells, showing their interaction with endogenous KPTN and OTUD3, respectively ( xref )."
38288086
sparser
"The western blot results showed protein bands bound to Flag‐OTUD3 (Figure  xref )."
40462502
OTUD3 inhibits Endoplasmic Reticulum Stress. 6 / 6
| 6
reach
"Fortilin Alleviated OTUD3 Knockdown Induced ER Stress."
37107185
reach
"Downregulation of OTUD3 reduced the binding ability of Fortilin to IRE1α, thereby activating the IRE1α pathway and inducing ER stress and neuronal apoptosis."
37107185
reach
"In the present study, our results demonstrated that OTUD3 knockdown-induced ER stress and cell apoptosis through the activation of the IRE1α pathway but not the PERK or ATF6α pathways."
37107185
reach
"Our data indicated that the ER stress caused by OTUD3 knockdown might be related the Fortilin expression."
37107185
reach
"These results suggested that OTUD3 knockdown would induce ER stress in dopaminergic neurons both in vivo and in vitro."
37107185
reach
"To explore which ER stress pathway was activated by OTUD3 knockdown, we detected the protein expression of the three pathways separately."
37107185
reach
"Furthermore, we explored OTUD3-induced ER stress through IRE1α pathway, which was caused by the deubiquitination of Fortilin."
37107185
OTUD3 affects ACTN4
1 | 4 2
OTUD3 binds ACTN4.
1 | 1 2
OTUD3 binds ACTN4. 4 / 4
1 | 1 2
sparser
"Further studies found that OTUD3 directly binds to ACTN4, leading to its deubiquitination and stabilization."
40607251
reach
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
34380780
biogrid
No evidence text available
34380780
sparser
"This dualism—both restraining and driving HCC malignancy—illustrates the nuanced, pleiotropic functions of OTUD3 and highlights the OTUD3-ACTN4 axis as a promising target for controlling advanced HCC (Table xref )."
41437362
OTUD3 deubiquitinates ACTN4.
| 2
OTUD3 deubiquitinates ACTN4. 2 / 2
| 2
reach
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
34380780
reach
"OTUD3 mediates Alpha-actinin 4 ACTN4 deubiquitination in HCC to stabilize it and promote hepatocellular carcinoma cell growth and metastasis (Xie et al., 2021)."
37829187
OTUD3 activates ACTN4.
| 1
OTUD3 activates ACTN4. 1 / 1
| 1
reach
"OTUD3 promotes lung tumorigenesis by stabilizing GRP78 [44], while it stabilizes ACTN4 to drive hepatocellular carcinoma progression and metastasis [45]."
38351178
MAVS affects OTUD3
| 4 3
MAVS binds OTUD3.
| 3 3
OTUD3 binds MAVS. 4 / 4
| 1 3
sparser
"Furthermore, OTUD3 immunoprecipitated together with MAVS in untransfected peritoneal macrophages, BMDMs, and MEFs ( Figure 3 H), which showed that endogenous MAVS is associated with OTUD3."
32679077
sparser
"19 According to the study showing that OTUD3 associates with mitochondrial antiviral-signaling protein (MAVS) to suppress anti-RNA viral immune response, 17 we also performed coIP experiments using F[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
reach
"Interestingly, a time-course analysis of SeV infection showed that, concomitant with the increased binding of MAVS to TRIM31, the association between MAVS and OTUD3 remained actually constant ( Figure[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal ( xref )."
36505476
OTUD3-C76S binds MAVS. 1 / 1
| 1
reach
"As shown in Figure 3 D, it is obvious that OTUD3 C76S associates with both MAVS and cGAS, which is different from the reported result stating that cGAS did not interact with OTUD3 C76S but MAVS did."
36966392
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
MAVS inhibits OTUD3.
| 1
MAVS inhibits OTUD3. 1 / 1
| 1
reach
"It seems that at resting states, the levels of MAVS-K63-linked ubiquitination remain low by OTUD3, while upon viral infection, OTUD3 is inactivated by SIRT1-mediated K129 deacetylation, allowing for the buildup of K63-linked ubiquitination of MAVS for its activation (158)."
35795661
Flag affects OTUD3
| 7
OTUD3 binds Flag. 7 / 7
| 7
sparser
"Flag-OTUD3 and His-BHLHE22 vectors were co-transfected into 293 T cells to verify exogenous OTUD3 and BHLHE22 protein interaction (Fig.  xref d)."
41484895
sparser
"Flag-OTUD3 WT or Flag-OTUD3 C76A , Myc-GRP78, and HA-Ub were transfected into HEK293T cells as indicated."
37369659
sparser
"Flag-OTUD3 WT (wild-type) or Flag-OTUD3 C76A, Myc-GRP78 and HA-Ub were transfected into HEK293T cells as indicated."
38539203
sparser
"Compared with the IgG control group, 17 proteins with a difference >4‐fold in the Flag‐OTUD3 group were initially screened as interacting proteins of OTUD3."
40462502
sparser
"Additionally, we validated this interaction by reciprocal experiments, where we overexpressed KPTN-Myc and OTUD3-Flag and obtained similar results ( xref )."
38288086
sparser
"Further confirmation involved separate overexpression of KPTN-Flag and OTUD3-Flag in HEK-293T cells, showing their interaction with endogenous KPTN and OTUD3, respectively ( xref )."
38288086
sparser
"The western blot results showed protein bands bound to Flag‐OTUD3 (Figure  xref )."
40462502
Nicotine affects OTUD3
| 1 5
Nicotine inhibits OTUD3.
| 1 1
Nicotine inhibits OTUD3. 2 / 2
| 1 1
reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
34853315
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 ."
34853315
Nicotine decreases the amount of OTUD3.
| 2
Nicotine decreases the amount of OTUD3. 2 / 2
| 2
reach
"For instance, nicotine has been shown to increase VEGF-C levels in ESCC and influence lymphatic metastasis by reducing the expression of OTUD3, thereby inhibiting the ability of ZEP36 to bind to specific regions of VEGF-C mRNA and causing its decline (77)."
37359527
reach
"Downregulation of OTUD3 expression by Nicotine in esophageal cancer leads to downregulation of ZFP36, which induces VEGF-C production and promotes lymphatic metastasis in esophageal cancer (Wang et al., 2021) (Figure 2D)."
37829187
Nicotine increases the amount of OTUD3.
| 1
Nicotine increases the amount of OTUD3. 1 / 1
| 1
reach
"Downregulation of OTUD3 expression by Nicotine in esophageal cancer leads to downregulation of ZFP36, which induces VEGF-C production and promotes lymphatic metastasis in esophageal cancer (Wang et al., 2021) (Figure 2D)."
37829187
Nicotine activates OTUD3.
| 1
Nicotine activates OTUD3. 1 / 1
| 1
reach
"Wang et al. (2021) analyzed the relation between OTUD3 and lymphatic metastasis, and found that nicotine-mediated OTUD3 downregulation inhibited VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
38246894
Glucose affects OTUD3
| 4 2
Glucose acetylates OTUD3.
| 3 2
Glucose leads to the acetylation of OTUD3. 5 / 5
| 3 2
reach
"More importantly, we found that glucose and fatty acids can stimulate CREB-binding protein (CBP)-dependent OTUD3 acetylation and promote its nuclear translocation, where OTUD3 regulates various genes [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
sparser
"More importantly, we found that glucose and fatty acids can stimulate CREB-binding protein (CBP)-dependent OTUD3 acetylation and promote its nuclear translocation, where OTUD3 regulates various genes [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
reach
"We found that both glucose and FFA significantly increased OTUD3 acetylation levels in a dose-dependent manner ( Figure 6 C, lanes 2–4 versus lane 1; Figure S7 C, lanes 2–4 versus lane 1)."
35675826
reach
"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) (12)."
36531510
sparser
"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) ( xref )."
36531510
Glucose increases the amount of OTUD3.
| 1
Glucose increases the amount of OTUD3. 1 / 1
| 1
reach
"We found that both glucose and FFA significantly increased OTUD3 acetylation levels in a dose-dependent manner ( Figure 6 C, lanes 2–4 versus lane 1; Figure S7 C, lanes 2–4 versus lane 1)."
35675826
RIGI affects OTUD3
| 5 1
RIGI binds OTUD3.
| 3 1
OTUD3 binds RIGI. 3 / 3
| 2 1
reach
"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
reach
"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
35675783
sparser
"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
OTUD3 binds RIGI and K63. 1 / 1
| 1
reach
"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
RIGI inhibits OTUD3.
| 1
RIGI inhibits OTUD3. 1 / 1
| 1
reach
"Taken together, these data suggest that OTUD3 inhibits RNF135-induced RIG-I and TRIM65-induced MDA5 activation.To further investigate the roles of OTUD3 in vivo , we generated Otud3 -deficient mice by[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
RIGI activates OTUD3.
| 1
RIGI activates OTUD3. 1 / 1
| 1
reach
"Taken together, these data suggest that OTUD3 inhibits RNF135-induced RIG-I and TRIM65-induced MDA5 activation.To further investigate the roles of OTUD3 in vivo , we generated Otud3 -deficient mice by[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3
2 | 4
OTUD3 binds.
2 | 3
OTUD3 binds OTUD3. 5 / 5
2 | 3
biogrid
No evidence text available
26280536
biogrid
No evidence text available
26280536
reach
"Then, we confirmed that OTUDin3 bound to OTUD3 and inhibited the deubiquitinating activity of OTUD3 by interfering with Ub binding to OTUD3."
37369659
reach
"The results showed that OTUDin3 bound to OTUD3 with a dissociation equilibrium constant (KD) value of 0.32 μM (Fig. 1J)."
37369659
reach
"This implied that OTUDin3 bound to OTUD3 with a certain specificity.Next, we performed in vitro deubiquitination assays to verify whether OTUDin3 inhibits the deubiquitinating activity of OTUD3."
37369659
OTUD3 translocates.
| 1
OTUD3 translocates to the cytosol. 1 / 1
| 1
reach
"This result could partially explain the enhanced association between OTUD3 and cGAS in cells under DNA activation ( Figures 3 B and 3C), and also supports that OTUD3 can be recruited to cGAS-DNA compl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
OTUD3 affects Neoplasms
| 2 4
OTUD3 inhibits Neoplasms.
| 1 2
OTUD3 inhibits Neoplasms. 2 / 2
| 1 1
reach
"These experiments collectively confirmed that OTUD3 can suppress the growth and proliferation of tumor cells.Moreover, to corroborate these findings, we conducted CCK8 cell proliferation assays on HeLa-WT, OTUD3-GFP, OTUD3-KO, OTUD3-KO cells with exogenous expression of wild-type OTUD3 (OTUD3-KO+OTUD3-Myc), and OTUD3-KO cells with exogenous expression of catalytically inactive OTUD3 (OTUD3-KO+OTUD3-C76A-Myc)."
38288086
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 ."
32395534
OTUD3 bound to PTEN inhibits Neoplasms. 1 / 1
| 1
reach
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer (Yuan et al., 2015)."
37829187
OTUD3 activates Neoplasms.
| 1 2
OTUD3 activates Neoplasms. 3 / 3
| 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 ) ."
31266968
reach
"Importantly, we found that OTUD3 acts as an oncogene to accelerate CRC tumor growth by enhancing YY1 stability while YY1 depletion reversed OTUD3 overexpression-induced tumor progression."
38351178
reach
"To determine whether OTUD3 promotes tumor progression by regulating YY1, we restored the expression of YY1 in endogenous OTUD3 depletion CRC cells or knocked down endogenous YY1 in OTUD3-overexpressing CRC cells."
38351178
OTUD3 affects Neoplasm Metastasis
| 2 3
OTUD3 inhibits Neoplasm Metastasis.
| 2 1
OTUD3 inhibits Neoplasm Metastasis. 2 / 3
| 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 ) ."
31266968
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 ."
31266968
OTUD3 bound to PTEN inhibits Neoplasm Metastasis. 1 / 1
| 1
reach
"OTUD3 interacts with PTEN in the cytoplasm, deubiquitinates and stabilizes PTEN, ultimately inhibiting tumor growth and metastasis in breast cancer (Yuan et al., 2015)."
37829187
OTUD3 activates Neoplasm Metastasis.
| 2
OTUD3 activates Neoplasm Metastasis. 2 / 2
| 2
reach
"Finally, ACTN4 was found to be essential for OTUD3 mediated HCC proliferation and metastasis in vitro and in vivo."
34380780
reach
"However, in lung cancer, OTUD3 promotes tumour proliferation and metastasis and inhibits apoptosis through deubiquitination of GRP78 protein and is closely related to drug resistance (163)."
36969062
OTUD3 affects MYL12A
| 1 5
OTUD3 binds MYL12A.
| 5
OTUD3 binds MYL12A. 5 / 5
| 5
sparser
"Immunofluorescence showed OTUD3 and PD-L1 colocalization (Fig. xref ), and CO-IP experiments verified OTUD3’s interaction with MYL12A in Farage cells (Fig. xref )."
39097608
sparser
"OTUD3 interacts with MYL12A and rupatadine."
39097608
sparser
"However, rupatadine reduced MYL12A’s binding to wild-type OTUD3 (Fig. xref ), indicating that while the C76A mutation doesn’t affect binding, rupatadine can disrupt their interaction."
39097608
sparser
"Further CO-IP experiments confirmed OTUD3 and MYL12A interaction in Farage cells, with immunofluorescence showing their colocalization (Fig. xref )."
39097608
sparser
"Results showed the M2 region of OTUD3 (amino acids 53–196) primarily interacts with MYL12A’s M2 region (amino acids 18–171, Fig. xref )."
39097608
OTUD3 deubiquitinates MYL12A.
| 1
OTUD3 deubiquitinates MYL12A. 1 / 1
| 1
reach
"This operation diminishes the deubiquitination of both MYL12A and PD-L1 by OTUD3."
39097608
OTUD3 affects CREBBP
| 2 4
OTUD3 binds CREBBP. 6 / 6
| 2 4
sparser
"The data of that study suggested that the CREB-binding-protein-dependent OTUD3 (CBP–OTUD3) signaling pathway plays a key role in glucose and fatty acid metabolism."
36531510
sparser
"Also, increased interaction between CBP and OTUD3 was correlated with increases in glucose and fatty acid concentrations ( Figure S7 I, lanes 3–5 versus lane 2)."
35675826
sparser
"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) ( xref )."
36531510
reach
"Also, increased interaction between CBP and OTUD3 was correlated with increases in glucose and fatty acid concentrations ( Figure S7 I, lanes 3–5 versus lane 2)."
35675826
reach
"Additionally, we found that high glucose levels increase the interaction between OTUD3 and CBP."
35675826
sparser
"Additionally, we found that high glucose levels increase the interaction between OTUD3 and CBP."
35675826
reach
"To test this hypothesis, we transfected KPTN shRNA into PTEN-KO HeLa cells exogenously expressing OTUD3-Myc, observing whether OTUD3 could still inhibit the mTORC1 signaling pathway in the absence of both PTEN and KPTN."
38288086
reach
"The results showed that the ability of OTUD3 to inhibit the mTORC1 signaling pathway was significantly weakened under conditions of concurrent PTEN and KPTN depletion (Figure 4E)."
38288086
reach
"These findings partially confirm the essential role of the KPTN protein in OTUD3’s ability to downregulate the mTORC1 signaling pathway in cells."
38288086
reach
"3.3 OTUD3 downregulated mTORC1 signaling pathway on account of its enzymatic deubiquitinase activity."
38288086
reach
"This suggests that OTUD3C76A, lacking deubiquitinase activity, cannot reverse the upregulation of the mTORC1 signaling pathway caused by the knockout of endogenous OTUD3.In this section of the study, through a series of experiments involving amino acid starvation and stimulation in HeLa cells, we demonstrated that OTUD3 can downregulate the mTORC1 signaling pathway, and this downregulation is dependent on the enzymatic deubiquitinase activity of OTUD3."
38288086
OTUD3 affects glucose
| 5
OTUD3 activates glucose.
| 4
OTUD3 activates glucose. 4 / 4
| 4
reach
"Our previous study indicated that OTUD3 promoted lung tumorigenesis through stabilizing the glucose-regulated protein 78 kDa (GRP78) [2, 17]."
38539203
reach
"However, nuclear endogenous OTUD3 levels increased with FFA ( Figure 6 A, lanes 8–12 versus lane 7) or glucose ( Figure S7 A, lanes 9–11 versus lanes 7 and 8) stimulation in a dose-dependent manner in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
reach
"Nuclear OTUD3, in turn, promotes glucose and fatty acid metabolism through stabilized diverse energy-metabolism-related transcription factors."
35675826
reach
"Remarkably, OTUD3 promotes lung tumorigenesis by stabilizing the glucose-regulated protein 78 kDa (GRP78) [26], which is a multifunctional protein with activities far beyond its well-known role in controlling unfolded protein response and implicated in promoting tumor proliferation, metastasis and involved in drug resistance [30–36]."
37369659
OTUD3 deubiquitinates glucose.
| 1
OTUD3 leads to the deubiquitination of glucose. 1 / 1
| 1
reach
"The underlying mechanism is that OTUD3 induces the deubiquitination of glucose-regulated protein 78 (GRP78), and subsequently promotes tumor proliferation and metastasis (Qian et al., 2017; Shen et al., 2017)."
37251574
OTUD3 affects ferroptosis
| 5
OTUD3 inhibits ferroptosis.
| 4
OTUD3 inhibits ferroptosis. 4 / 4
| 4
reach
"In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Finally, through in vivo experimental verification, we verified the mechanism of this new pathway in IS; namely, overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway.In conclusion, we preliminarily evaluated the effects of the OTUD3/IRP2/p53/PTGS2 pathway on IS and determined whether its potential mechanism of action was related to ferroptosis."
39415292
reach
"These results suggested that the overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
OTUD3 activates ferroptosis.
| 1
OTUD3 bound to NFE2L2 activates ferroptosis. 1 / 1
| 1
reach
"We found that the recruitment of OTUD3 to NRF2 by BUB1b stabilized the protein level of NRF2 and enhanced resistance to ferroptosis, which conferred chemoresistance to LUAD."
39043653
OTUD3 affects ZNF598
| 5
OTUD3 inhibits ZNF598.
| 3
OTUD3 inhibits ZNF598. 3 / 3
| 3
reach
"These results are consistent with the hypothesis that USP21 and OTUD3 directly antagonize ZNF598-mediated RRub events."
32011234
reach
"Subsequent work supports this model, revealing that 40–100-fold overexpression of OTUD3 and USP2 is required to suppress ZNF598 function [21]."
36963992
reach
"First, USP21 and OTUD3 may limit the activity of ZNF598 and other RRub ligases through direct antagonism to prevent spurious RRub."
32011234
OTUD3 ubiquitinates ZNF598.
| 1
OTUD3 leads to the ubiquitination of ZNF598. 1 / 1
| 1
reach
"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]."
32050486
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."
32011234
OTUD3 affects TPT1
1 | 4
OTUD3 decreases the amount of TPT1.
| 2
OTUD3 decreases the amount of TPT1. 2 / 2
| 2
reach
"Ubiquitylation assays showed that OTUD3 knockdown significantly enhanced the ubiquitylation level of Fortilin in SH-SY5Y cells and HEK293T cells (Figure 5M,N)."
37107185
reach
"Overexpression of WT OTUD3, rather than the C76A mutant, reversed the decreased Fortilin level induced by OTUD3 knockdown (Figure 5Q)."
37107185
OTUD3 ubiquitinates TPT1.
| 1
OTUD3 leads to the ubiquitination of TPT1. 1 / 1
| 1
reach
"Our findings demonstrate that OTUD3 plays a crucial role in protecting cells against ER stress-induced apoptosis by regulating the level of ubiquitination of Fortilin and inhibiting the activation of IRE1α signaling."
37107185
OTUD3 binds TPT1.
1 |
TPT1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
37107185
OTUD3 activates TPT1.
| 1
OTUD3 activates TPT1. 1 / 1
| 1
reach
"Deubiquitylase OTUD3 Mediates Endoplasmic Reticulum Stress through Regulating Fortilin Stability to Restrain Dopaminergic Neurons Apoptosis."
37107185
OTUD3 affects STUB1
2 | 2 1
OTUD3 binds STUB1. 5 / 5
2 | 2 1
biogrid
No evidence text available
32483383
reach
"CHIP interacts with, polyubiquitylates OTUD3 and promotes OTUD3 degradation."
32483383
biogrid
No evidence text available
32483383
reach
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [98]."
38841185
sparser
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [ xref ]."
38841185
OTUD3 affects RPS20
| 5
OTUD3 ubiquitinates RPS20.
| 2
OTUD3 leads to the ubiquitination of RPS20. 2 / 2
| 2
reach
"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)."
34391779
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."
32011234
OTUD3 deubiquitinates RPS20.
| 2
OTUD3 deubiquitinates RPS20. 2 / 2
| 2
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."
32011234
reach
"USP21 and OTUD3 deubiquitylate ZNF598 substrates eS10 and uS10."
32011234
OTUD3 inhibits RPS20.
| 1
OTUD3 inhibits RPS20. 1 / 1
| 1
reach
"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)."
32011234
OTUD3 inhibits Neoplasm Invasiveness. 5 / 5
| 5
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion."
37369659
reach
"Collectively, these results demonstrated that OTUDin3 inhibited NSCLC cell growth, migration and invasion."
37369659
reach
"OTUDin3 inhibits NSCLC cell growth, migration and invasion, and induces apoptosis by targeting OTUD3."
37369659
reach
"Taken together, these results demonstrated that OTUDin3 inhibited lung cancer cell growth, migration and invasion, and induced apoptosis by targeting OTUD3."
37369659
reach
"OTUD3 can also be ubiquitinated by TRIM56, thereby inhibiting invasion and migration of lung adenocarcinoma (Marcotte et al., 2016) (Figure 3C)."
37829187
OTUD3 affects Death
| 5
OTUD3 activates Death.
| 3
OTUD3 activates Death. 2 / 2
| 2
reach
"The results indicated that Otud3 −/− mice were significantly more resistant to EMCV-induced death than the WT controls ( Figure 3 A )."
35675783
reach
"Reconstitution of WT otud3 , but not of otud3 (C70A) or GFP mRNA, in otud3 −/− embryos promoted SVCV-induced death ( Figures S7 K and S7L)."
35675783
OTUD3-C70A activates Death. 1 / 1
| 1
reach
"Reconstitution of WT otud3 , but not of otud3 (C70A) or GFP mRNA, in otud3 −/− embryos promoted SVCV-induced death ( Figures S7 K and S7L)."
35675783
OTUD3 inhibits Death.
| 2
OTUD3 inhibits Death. 2 / 2
| 2
reach
"Therefore, knockout of OTUD3 could upregulate the content of iron in dopaminergic neurons in the substantia nigra which, in turn, contributes to increased ER stress, and induces neuronal death and PD pathology."
37760024
reach
"Moreover, reconstitution of WT otud3 but not of otud3 -C70A or GFP mRNA in otud3 −/− embryos attenuated CyHV-2-induced death in otud3 −/− larvae ( Figures S9 D and S9E)."
35675783
MYL12A affects OTUD3
| 5
OTUD3 binds MYL12A. 5 / 5
| 5
sparser
"Immunofluorescence showed OTUD3 and PD-L1 colocalization (Fig. xref ), and CO-IP experiments verified OTUD3’s interaction with MYL12A in Farage cells (Fig. xref )."
39097608
sparser
"OTUD3 interacts with MYL12A and rupatadine."
39097608
sparser
"However, rupatadine reduced MYL12A’s binding to wild-type OTUD3 (Fig. xref ), indicating that while the C76A mutation doesn’t affect binding, rupatadine can disrupt their interaction."
39097608
sparser
"Further CO-IP experiments confirmed OTUD3 and MYL12A interaction in Farage cells, with immunofluorescence showing their colocalization (Fig. xref )."
39097608
sparser
"Results showed the M2 region of OTUD3 (amino acids 53–196) primarily interacts with MYL12A’s M2 region (amino acids 18–171, Fig. xref )."
39097608
Bisphenol A affects OTUD3
4 |
Bisphenol A increases the amount of OTUD3.
2 |
Bisphenol A increases the amount of OTUD3. 2 / 2
2 |
ctd
No evidence text available
34947998
ctd
No evidence text available
25594700
Bisphenol A demethylates OTUD3.
1 |
Bisphenol A demethylates OTUD3. 1 / 1
1 |
ctd
No evidence text available
30906313
Bisphenol A decreases the amount of OTUD3.
1 |
Bisphenol A decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
33221593
UBC affects OTUD3
4 |
OTUD3 binds UBC. 4 / 4
4 |
biogrid
No evidence text available
27066941
biogrid
No evidence text available
29576527
biogrid
No evidence text available
23827681
biogrid
No evidence text available
34129829
TOP2A affects OTUD3
| 2 2
OTUD3 binds TOP2A. 4 / 4
| 2 2
sparser
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay ( xref lane 6)."
26657567
reach
"Direct interaction between OTUD3 and TOP2A was confirmed by an in vitro binding assay (XREF_FIG lane 6)."
26657567
reach
"We sought to determine which of these PTEN associated deubiquitinases associate with TOP2A, and found OTUD3 can associate with TOP2A."
26657567
sparser
"This association of OTUD3 and TOP2A was confirmed in MEFs and HCT116 cells ( xref lane 2, 4f lane 3)."
26657567
OTUD3 affects UBC
4 |
OTUD3 binds UBC. 4 / 4
4 |
biogrid
No evidence text available
27066941
biogrid
No evidence text available
29576527
biogrid
No evidence text available
23827681
biogrid
No evidence text available
34129829
reach
"These results suggested that the overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"In vivo, after overexpressing OTUD3 and knocking down IRP2, we found that overexpression of OTUD3 promoted IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway."
39415292
reach
"Finally, through in vivo experimental verification, we verified the mechanism of this new pathway in IS; namely, overexpression of OTUD3 induced IRP2 expression to reduce ferroptosis in hippocampal neurons and improve cerebral I/R injury via the inhibition of the p53/PTGS2 pathway.In conclusion, we preliminarily evaluated the effects of the OTUD3/IRP2/p53/PTGS2 pathway on IS and determined whether its potential mechanism of action was related to ferroptosis."
39415292
OTUD3 affects IFIH1
| 4
OTUD3 inhibits IFIH1. 4 / 4
| 4
reach
"These findings suggest that OTUD3 inhibits the oligomerization of RIG-I and MDA5 and prevents the binding of viral RNA to RIG-I and MDA5.To determine the functional role of OTUD3 in the activation of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
reach
"Coinciding with these observations, the overexpression of OTUD3 markedly inhibited the self-association of RIG-I and MDA5, as well as the association of MAVS with RIG-I or MDA5 ( Figures S4 E–S4H)."
35675783
reach
"These results suggest that OTUD3 deubiquitinates K63-linked polyubiquitination of RIG-I and MDA5.Overexpression of OTUD3 in HEK293T cells inhibited the oligomerization of RIG-I or MDA5 when these were[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
reach
"In contrast, knockdown OTUD3 in HEK293T by CRISPR-Cas9 cells enhanced the self-association of RIG-I and MDA5, and the association of MAVS with RIG-I or RIG-I or MDA5 ( Figures S4 I–S4L)."
35675783
OTUD3 affects CRC
| 4
OTUD3 activates CRC. 4 / 4
| 4
reach
"Therefore, we postulated that OTUD3 promotes CRC progression by up-regulating YY1."
38351178
reach
"Conversely, depletion of endogenous YY1 suppressed the OTUD3-induced CRC proliferation (Fig. 4C)."
38351178
reach
"Our findings suggest that OTUD3 promotes CRC progression by up-regulating YY1, and provides insights into the underlying mechanisms of YY1 over-expression in CRC."
38351178
reach
"OTUD3 accelerates CRC progression by up-regulating YY1."
38351178
OTUD3 affects AKT
| 4
OTUD3 inhibits AKT.
| 3
OTUD3 inhibits AKT. 3 / 3
| 3
reach
"OTUD3 inhibits the activation of the AKT pathway by deubiquitinating PTEN and suppresses tumour progression in breast cancer (BC), colon cancer and cervical cancer [45]."
38685067
reach
"It is speculated that OTUD3 function may be impaired in SCCs, destabilizing the tumor suppressor PTEN and thus activating the AKT pathway to cause cancer (Gatti et al., 2020)."
37829187
reach
"MiR-520h binds to the 3′-untranslated region (3′-UTR) of OTUD3 and inhibits OTUD3 protein expression, which in turn inhibits PTEN expression and ultimately activates the downstream pathway AKT."
37829187
OTUD3 activates AKT.
| 1
OTUD3 activates AKT. 1 / 1
| 1
reach
"MiR-520h binds to the 3′-untranslated region (3′-UTR) of OTUD3 and inhibits OTUD3 protein expression, which in turn inhibits PTEN expression and ultimately activates the downstream pathway AKT."
37829187
KPTN affects OTUD3
1 | 3
OTUD3 binds KPTN. 4 / 4
1 | 3
reach
"Our experiments indicated that the OTU domain plays a pivotal role in the interaction between OTUD3 and KPTN (Figures 1D, E)."
38288086
biogrid
No evidence text available
33961781
reach
"Through this method, we found that there is a potential interaction between the deubiquitinating enzyme OTUD3 and KPTN, which is one of the components of the KICSTOR protein complex, an important regulatory factor in the mTORC1 signaling pathway.Researchers have identified gene mutations in the breast cancer cell lines involving OTUD3, leading to loss of protein function and accelerating the migration and metastasis of cancer cells."
38288086
reach
"Thus, these results validated the interaction between OTUD3 and KPTN."
38288086
ACTN4 affects OTUD3
1 | 1 2
OTUD3 binds ACTN4. 4 / 4
1 | 1 2
sparser
"Further studies found that OTUD3 directly binds to ACTN4, leading to its deubiquitination and stabilization."
40607251
reach
"Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it."
34380780
biogrid
No evidence text available
34380780
sparser
"This dualism—both restraining and driving HCC malignancy—illustrates the nuanced, pleiotropic functions of OTUD3 and highlights the OTUD3-ACTN4 axis as a promising target for controlling advanced HCC (Table xref )."
41437362
Pirinixic acid affects OTUD3
3 |
Pirinixic acid increases the amount of OTUD3.
1 |
Pirinixic acid increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
23811191
Pirinixic acid decreases the amount of OTUD3.
1 |
Pirinixic acid decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
19710929
Pirinixic acid activates OTUD3.
1 |
Pirinixic acid activates OTUD3. 1 / 1
1 |
ctd
No evidence text available
19710929
Paracetamol affects OTUD3
3 |
Paracetamol increases the amount of OTUD3. 3 / 3
3 |
ctd
No evidence text available
33387578
ctd
No evidence text available
29067470
ctd
No evidence text available
21420995
MiR-32 affects OTUD3
| 3
MiR-32 activates OTUD3.
| 2
MiR-32 activates OTUD3. 2 / 2
| 2
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."
31338872
reach
"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."
31338872
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."
31338872
ZFP36 affects OTUD3
2 | 1
ZFP36 binds OTUD3. 3 / 3
2 | 1
biogrid
No evidence text available
34853315
sparser
"For example, OTUD3 interacts with the ZFP36 ring finger protein through its OTU region and stabilizes it by inhibiting FBXW7-mediated ubiquitination, which in turn induces VEGF-C mRNA decay to prevent lymphatic metastasis of human esophageal cancer xref ."
36385557
biogrid
No evidence text available
34853315
Protease affects OTUD3
| 2 1
Protease binds OTUD3.
| 1 1
OTUD3 binds Protease. 2 / 2
| 1 1
reach
"In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1."
38351178
sparser
"OTU deubiquitinase 3 (OTUD3) binds to the ovarian tumor-related protease family, PTEN protector."
36727069
Protease deubiquitinates OTUD3.
| 1
Protease deubiquitinates OTUD3. 1 / 1
| 1
reach
"Very recently, ovarian tumor protease (OTU) deubiquitinating enzyme 3 (OTUD3), a deubiquitination enzyme, was reported to bind to MDA5 and RIG-I and ultimately remove their Lys-63-linked polyubiquitination to diminish the signal transduction of RLRs, thus inhibiting the antiviral immune response against RNA viruses (Figure 2) [108]."
36980296
PPARD affects OTUD3
2 | 1
OTUD3 binds PPARD. 2 / 2
2 |
biogrid
No evidence text available
35675826
biogrid
No evidence text available
35675826
OTUD3 binds PPARD. 1 / 1
| 1
sparser
"Furthermore, we found glucose promoted the interaction between OTUD3 and PPARδ ( Figure 5 B, exogenous OTUD3, lanes 3 and 4 versus lane 2; Figure 5 C, endogenous OTUD3, lanes 3–5 versus lane 2)."
35675826
OTUD3 affects ZFP36
2 | 1
ZFP36 binds OTUD3. 3 / 3
2 | 1
biogrid
No evidence text available
34853315
sparser
"For example, OTUD3 interacts with the ZFP36 ring finger protein through its OTU region and stabilizes it by inhibiting FBXW7-mediated ubiquitination, which in turn induces VEGF-C mRNA decay to prevent lymphatic metastasis of human esophageal cancer xref ."
36385557
biogrid
No evidence text available
34853315
OTUD3 affects SLC7A11
| 1 2
OTUD3 binds SLC7A11.
| 2
SLC7A11 binds OTUD3. 2 / 2
| 2
sparser
"This mechanism not only positions OTUD3 at the nexus of iron metabolism and cell survival but also highlights the OTUD3-SLC7A11 axis as a promising therapeutic target for overcoming drug resistance in ccRCC."
41437362
sparser
"This OTUD3-SLC7A11 axis enhances cystine uptake, facilitates glutathione synthesis, and suppresses deleterious lipid peroxidation, ultimately inhibiting ferroptosis [ xref ]."
41437362
OTUD3 increases the amount of SLC7A11.
| 1
OTUD3 increases the amount of SLC7A11. 1 / 1
| 1
reach
"Immunoblotting results showed that the knockdown of OTUD3 in A549 cells with erastin decreased the expression of GPX4, HO-1, and xCT (Fig. 5H)."
39043653
OTUD3 affects SIRT1
| 1 2
OTUD3 binds SIRT1. 3 / 3
| 1 2
sparser
"Among the seven sirtuins (SIRT1–7) we have tested, co-expressed OTUD3 associated strongly with SIRT1 and weakly with SIRT7 ( Figure 6 C)."
32679077
sparser
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
reach
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 affects Parkinson Disease
| 3
OTUD3 inhibits Parkinson Disease.
| 2
OTUD3 inhibits Parkinson Disease. 2 / 2
| 2
reach
"Deubiquitylase OTUD3 prevents Parkinson's disease through stabilizing iron regulatory protein 2."
35490179
reach
"Therefore, knockout of OTUD3 could upregulate the content of iron in dopaminergic neurons in the substantia nigra which, in turn, contributes to increased ER stress, and induces neuronal death and PD pathology."
37760024
OTUD3 activates Parkinson Disease.
| 1
reach
"Therefore, targeting the inhibition of IRE1α signal activation could represent a promising therapeutic for PD induced by OTUD3 elimination."
37107185
OTUD3 affects PPARD
2 | 1
OTUD3 binds PPARD. 2 / 2
2 |
biogrid
No evidence text available
35675826
biogrid
No evidence text available
35675826
OTUD3 binds PPARD. 1 / 1
| 1
sparser
"Furthermore, we found glucose promoted the interaction between OTUD3 and PPARδ ( Figure 5 B, exogenous OTUD3, lanes 3 and 4 versus lane 2; Figure 5 C, endogenous OTUD3, lanes 3–5 versus lane 2)."
35675826
OTUD3 affects PI3K
| 3
OTUD3 ubiquitinates PI3K.
| 1
OTUD3 leads to the ubiquitination of PI3K. 1 / 1
| 1
reach
"Several studies have demonstrated that OTUD3 interacts with PTEN and induces its deubiquitination, increasing PTEN protein stability and inhibiting carcinogenic PI3K/AKT signaling (89)."
40337608
OTUD3 inhibits PI3K.
| 1
OTUD3 inhibits PI3K. 1 / 1
| 1
reach
"OTUD3 loss of function increases the Ub-dependent degradation of PTEN and enhances PI3K/AKT signaling in breast cancer cells ( Yuan et al., 2015 )."
35675826
OTUD3 binds PI3K.
| 1
OTUD3 binds PI3K. 1 / 1
| 1
reach
"Several studies have demonstrated that OTUD3 interacts with PTEN and induces its deubiquitination, increasing PTEN protein stability and inhibiting carcinogenic PI3K/AKT signaling (89)."
40337608
OTUD3 affects Interferon
| 3
OTUD3 inhibits Interferon.
| 2
OTUD3 inhibits Interferon. 2 / 2
| 2
reach
"Moreover, overexpression of OTUD3 dose-dependently suppressed Sendai virus (SeV)-induced IFNβ promoter activity in HEK293T cells ( Figure 1 B)."
35675783
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)."
34566944
OTUD3 activates Interferon.
| 1
OTUD3 activates Interferon. 1 / 1
| 1
reach
"In contrast, knockdown of OTUD3 by CRISPR-Cas9 (OTUD3-KD#1 and OTUD3-KD#2) in HEK293T cells enhanced its activity ( Figure 1 C), as well as the SeV-induced IFNβ promoter activity ( Figure 1 D)."
35675783
OTUD3 affects HNF1B
1 | 2
OTUD3 binds HNF1B. 3 / 3
1 | 2
sparser
"More importantly, unlike the WT form, the 4CS mutant HNF1B could not be succinated by DMF (Fig. xref ), and DMF impaired the interaction between OTUD3 and WT HNF1B, while there was no detectable change in the interaction between OTUD3 and 4CS mutant HNF1B upon DMF treatment (Fig. xref )."
39915461
biogrid
No evidence text available
35675826
sparser
"Collectively, these data suggest that OTUD3 binds to and stabilizes HNF1B, and that DMF treatment impairs this interaction, thereby promoting the degradation of HNF1B via ubiquitin-proteasome pathway."
39915461
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 ) ."
31266968
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 ) ."
31266968
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 ."
31266968
OTUD3 affects Deubiquitinase
| 3
OTUD3 activates Deubiquitinase.
| 2
OTUD3 activates Deubiquitinase. 2 / 2
| 2
reach
"Mechanistically, acetylation of the core OTU domain in OTUD3 markedly enhances deubiquitinase activity on MAVS (mitochondrial antiviral-signaling protein), thereby inhibiting the innate antiviral immune response."
36385557
reach
"While OTUD3 acetylation promotes its DUB activity, its deacetylation by SIRT1 inhibits MAVS deubiquitination following viral infection, thus promoting activation of innate immune signaling (162)."
35764170
OTUD3 inhibits Deubiquitinase.
| 1
OTUD3 inhibits Deubiquitinase. 1 / 1
| 1
reach
"3.3 OTUD3 downregulated mTORC1 signaling pathway on account of its enzymatic deubiquitinase activity."
38288086
OTUD3 affects CD274
| 1 2
OTUD3 binds CD274.
| 2
OTUD3 binds CD274. 2 / 2
| 2
sparser
"In HEK293T cells, His-tagged PD-L1 bound both wild-type and C76A mutant OTUD3 with Flag tags (Fig. xref ), and like MYL12A, PD-L1’s binding to wild-type OTUD3 decreased with rupatadine, indicating the C76A mutation doesn’t affect PD-L1 binding, but rupatadine can disrupt it."
39097608
sparser
"Importantly, we found that OTUD3’s interaction with PD-L1 contributes to CD8+ T cell exhaustion."
39097608
OTUD3 deubiquitinates CD274.
| 1
OTUD3 deubiquitinates CD274. 1 / 1
| 1
reach
"This operation diminishes the deubiquitination of both MYL12A and PD-L1 by OTUD3."
39097608
OTUD3 affects BUB1B
| 2 1
OTUD3 binds BUB1B. 2 / 2
| 1 1
reach
"Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy."
39043653
sparser
"Co-IP assays with OTUD3 and BUB1b antibodies confirmed that OTUD3 and BUB1b could interact with each other (Fig. xref )."
39043653
BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
reach
"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
OTUD3 affects ARID3A
| 2 1
OTUD3 inhibits ARID3A.
| 1
OTUD3 inhibits ARID3A. 1 / 1
| 1
reach
"In conclusion, GSK3β phosphorylates OTUD3, enhances its binding ability to ARID3A, and ultimately inhibits the ubiquitination degradation of ARID3A, which promotes the progression of CCA."
40181152
OTUD3 binds ARID3A.
| 1
ARID3A binds OTUD3. 1 / 1
| 1
sparser
"A well-characterized example involves GSK3β-mediated phosphorylation at Ser9, which promotes OTUD3 binding to the transcription factor ARID3A. This interaction facilitates ARID3A deubiquitination and stabilization, driving proliferation and metastasis in cholangiocarcinoma (CCA)."
41437362
OTUD3 activates ARID3A.
| 1
OTUD3 activates ARID3A. 1 / 1
| 1
reach
"OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
HNF1B affects OTUD3
1 | 2
OTUD3 binds HNF1B. 3 / 3
1 | 2
sparser
"More importantly, unlike the WT form, the 4CS mutant HNF1B could not be succinated by DMF (Fig. xref ), and DMF impaired the interaction between OTUD3 and WT HNF1B, while there was no detectable change in the interaction between OTUD3 and 4CS mutant HNF1B upon DMF treatment (Fig. xref )."
39915461
biogrid
No evidence text available
35675826
sparser
"Collectively, these data suggest that OTUD3 binds to and stabilizes HNF1B, and that DMF treatment impairs this interaction, thereby promoting the degradation of HNF1B via ubiquitin-proteasome pathway."
39915461
CRISPR-Cas9 affects OTUD3
| 3
CRISPR-Cas9 inhibits OTUD3. 3 / 3
| 3
reach
"The efficiency of OTUD3 knockdown mediated by CRISPR-Cas9 (OTUD3 KD#1 and OTUD3 KD#2) was confirmed by western blotting ( Figure S2 E)."
35675783
reach
"In contrast, knockdown of OTUD3 by CRISPR-Cas9 (OTUD3-KD #2) in HEK293T cells enhanced K63-linked polyubiquitination in the absence of viral infection ( Figures 2 C and 2D) and in the presence of SeV [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
reach
"In contrast, knockdown of OTUD3 by CRISPR-Cas9 (OTUD3-KD#1 and OTUD3-KD#2) in HEK293T cells enhanced its activity ( Figure 1 C), as well as the SeV-induced IFNβ promoter activity ( Figure 1 D)."
35675783
BUB1B affects OTUD3
| 2 1
OTUD3 binds BUB1B. 2 / 2
| 1 1
reach
"Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy."
39043653
sparser
"Co-IP assays with OTUD3 and BUB1b antibodies confirmed that OTUD3 and BUB1b could interact with each other (Fig. xref )."
39043653
BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
reach
"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
VIRF-2 affects OTUD3
| 2
OTUD3 binds vIRF-2. 2 / 2
| 2
sparser
"Additionally, an S2 site on OTUD3 interacting with K11-linked terminal diUb probes was found to provide the linkage specificity."
| PMC
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."
27066941
Titanium dioxide affects OTUD3
2 |
Titanium dioxide demethylates OTUD3.
1 |
Titanium dioxide demethylates OTUD3. 1 / 1
1 |
ctd
No evidence text available
35295148
Titanium dioxide decreases the amount of OTUD3.
1 |
Titanium dioxide decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
29264374
Thioacetamide affects OTUD3
2 |
Thioacetamide increases the amount of OTUD3. 2 / 2
2 |
ctd
No evidence text available
34492290
ctd
No evidence text available
23411599
Sodium arsenite affects OTUD3
2 |
Sodium arsenite increases the amount of OTUD3. 2 / 2
2 |
ctd
No evidence text available
38568856
ctd
No evidence text available
29361514
Ozone affects OTUD3
2 |
Ozone increases the amount of OTUD3.
1 |
Ozone increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Ozone decreases the amount of OTUD3.
1 |
Ozone decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
MiR-520h affects OTUD3
| 2
MiR-520h decreases the amount of OTUD3.
| 1
MiR-520h bound to OTUD3 decreases the amount of OTUD3. 1 / 1
| 1
reach
"For example, miR-520h binds to OTUD3 to inhibit the expression of OTUD3 protein in breast cancer cells, which in turn enhances the resistance of breast cancer cells to paclitaxel (Geng et al., 2020)."
37829187
MiR-520h binds OTUD3.
| 1
MiR-520h binds OTUD3. 1 / 1
| 1
reach
"For example, miR-520h binds to OTUD3 to inhibit the expression of OTUD3 protein in breast cancer cells, which in turn enhances the resistance of breast cancer cells to paclitaxel (Geng et al., 2020)."
37829187
Methyl methanesulfonate increases the amount of OTUD3. 2 / 2
2 |
ctd
No evidence text available
23649840
ctd
No evidence text available
26011545
Methacrylaldehyde affects OTUD3
2 |
Methacrylaldehyde increases the amount of OTUD3.
1 |
Methacrylaldehyde increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Methacrylaldehyde decreases the amount of OTUD3.
1 |
Methacrylaldehyde decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Fatty acid affects OTUD3
| 2
Fatty acid acetylates OTUD3. 2 / 2
| 2
sparser
"More importantly, we found that glucose and fatty acids can stimulate CREB-binding protein (CBP)-dependent OTUD3 acetylation and promote its nuclear translocation, where OTUD3 regulates various genes [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
sparser
"Glucose and fatty acids can stimulate CBP–OTUD3 acetylation, thus promoting nuclear translocation, wherein OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARd) ( xref )."
36531510
Apoptotic process affects OTUD3
| 2
Apoptotic process inhibits OTUD3.
| 1
Apoptotic process inhibits OTUD3. 1 / 1
| 1
reach
"In our present study, we identified Rolapitant as an inhibitor of OTUD3 that can also promote ER stress DR5-induced apoptosis of lung cancer cells through disrupting the interaction of OTUD3 with GRP78.Apoptosis includes the extrinsic and intrinsic apoptotic pathways."
38539203
Apoptotic process activates OTUD3.
| 1
reach
"In our present study, we identified Rolapitant as an inhibitor of OTUD3 that can also promote ER stress DR5-induced apoptosis of lung cancer cells through disrupting the interaction of OTUD3 with GRP78.Apoptosis includes the extrinsic and intrinsic apoptotic pathways."
38539203
Alpha-pinene affects OTUD3
2 |
Alpha-pinene increases the amount of OTUD3.
1 |
Alpha-pinene increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Alpha-pinene decreases the amount of OTUD3.
1 |
Alpha-pinene decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Acrolein affects OTUD3
2 |
Acrolein increases the amount of OTUD3.
1 |
Acrolein increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Acrolein decreases the amount of OTUD3.
1 |
Acrolein decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
USP25 affects OTUD3
| 2
OTUD3 binds USP25. 2 / 2
| 2
sparser
"Importantly, both OTUD3 and USP21 are present in the ribosome pellet fraction suggesting that OTUD3 and USP21 associates with ribosomes."
32011234
sparser
"Given the ability of USP21 and OTUD3 to remove RRub events, we examined if OTUD3 or USP21 associated with ribosomes."
32011234
USP13 affects OTUD3
| 2
USP11 binds USP13 and OTUD3. 1 / 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 )."
30733438
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."
32140262
TRIM56 affects OTUD3
| 1 1
TRIM56 ubiquitinates OTUD3. 2 / 2
| 1 1
sparser
"OTUD3 can also be ubiquitinated by TRIM56, thereby inhibiting invasion and migration of lung adenocarcinoma ( xref ) ( xref )."
37829187
reach
"OTUD3 can also be ubiquitinated by TRIM56, thereby inhibiting invasion and migration of lung adenocarcinoma (Marcotte et al., 2016) (Figure 3C)."
37829187
TRIM25 affects OTUD3
2 |
TRIM25 binds OTUD3. 2 / 2
2 |
biogrid
No evidence text available
31266968
biogrid
No evidence text available
29117863
STF-083010 affects OTUD3
| 2
STF-083010 inhibits OTUD3.
| 1
STF-083010 inhibits OTUD3. 1 / 1
| 1
reach
"STF-083010 treatment also inhibited the cell apoptosis of OTUD3 knockdown cells but partially reversed apoptosis after STF-083010 treatment (Figure 4P,Q)."
37107185
STF-083010 activates OTUD3.
| 1
STF-083010 activates OTUD3. 1 / 1
| 1
reach
"The ratio of p-IRE1alpha/IRE1alpha, and the expression of X-box binding protein 1-spliced (XBP1s) were remarkably increased after OTUD3 knockdown, which was inhibited by IRE1alpha inhibitor STF-083010 treatment."
37107185
SLC7A11 affects OTUD3
| 2
SLC7A11 binds OTUD3. 2 / 2
| 2
sparser
"This mechanism not only positions OTUD3 at the nexus of iron metabolism and cell survival but also highlights the OTUD3-SLC7A11 axis as a promising therapeutic target for overcoming drug resistance in ccRCC."
41437362
sparser
"This OTUD3-SLC7A11 axis enhances cystine uptake, facilitates glutathione synthesis, and suppresses deleterious lipid peroxidation, ultimately inhibiting ferroptosis [ xref ]."
41437362
SIRT7 affects OTUD3
| 1 1
OTUD3 binds SIRT7. 2 / 2
| 1 1
reach
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD4 affects OTUD3
1 | 1
OTUD3 binds OTUD4. 2 / 2
1 | 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
biogrid
No evidence text available
31266968
OTUD3 affects δ
| 2
OTUD3 deubiquitinates δ.
| 1
OTUD3 deubiquitinates δ. 1 / 1
| 1
reach
"OTUD3 also deubiquitinates and stabilizes PPARδ to regulate energy metabolism and obesity [18]."
36672466
OTUD3 decreases the amount of δ.
| 1
OTUD3 decreases the amount of δ. 1 / 1
| 1
reach
"Consistent with this finding, knockdown of Otud3 in HEK293T cells showed increased ubiquitination levels of PPARδ ( Figure S6 D, lanes 2 and 3 versus lane 1), and exogenous expression of WT OTUD3, but[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD3 affects vIRF-2
| 2
OTUD3 binds vIRF-2. 2 / 2
| 2
sparser
"Additionally, an S2 site on OTUD3 interacting with K11-linked terminal diUb probes was found to provide the linkage specificity."
| PMC
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."
27066941
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 ."
31266968
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 ."
31266968
OTUD3 affects pathway
| 2
OTUD3 inhibits pathway. 2 / 2
| 2
sparser
"In this study, multiple experiments were conducted to verify whether OTUD3 can inhibit TGF-β pathway by deubiquitinating SMAD7."
40382618
sparser
"Furthermore, luciferase reporting assay, in vitro protein interaction, and transwell assay were used to verify whether OTUD3 could inhibit TGF-β pathway by deubiquitinating SMAD7 and affect cell invasion."
40382618
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 ) ."
31266968
eidos
"OTUD3 promotes lung cancer cell growth and migration via GRP78 ."
31266968
reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
34853315
reach
"Wang et al. (2021) analyzed the relation between OTUD3 and lymphatic metastasis, and found that nicotine-mediated OTUD3 downregulation inhibited VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
38246894
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 ) ."
31266968
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 ."
31266968
OTUD3 affects iron atom
| 2
OTUD3 inhibits iron atom.
| 1
OTUD3 inhibits iron atom. 1 / 1
| 1
reach
"Therefore, knockout of OTUD3 could upregulate the content of iron in dopaminergic neurons in the substantia nigra which, in turn, contributes to increased ER stress, and induces neuronal death and PD pathology."
37760024
OTUD3 deubiquitinates iron atom.
| 1
OTUD3 deubiquitinates iron atom. 1 / 1
| 1
reach
"OTUD3, a deubiquitinating enzyme of IRP2, interacts with IRP2 in the cytoplasm, and deubiquitinates and stabilizes the IRP2 protein in an iron-independent manner."
39415292
OTUD3 affects helicase
| 2
OTUD3 deubiquitinates helicase.
| 1
OTUD3 leads to the deubiquitination of helicase. 1 / 1
| 1
reach
"We further confirmed that overexpression of OTUD3 reduced K63-linked polyubiquitination of CARD and helicase domains of RIG-I and MDA5 ( Figures S3 C–S3F), implying that the deubiquitination of RIG-I [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 binds helicase.
| 1
Helicase binds OTUD3 and CTD domains. 1 / 1
| 1
reach
"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
35675783
OTUD3 affects cell death
| 2
OTUD3 inhibits cell death.
| 1
OTUD3 inhibits cell death. 1 / 1
| 1
reach
"We further explored the mode of cell death induced by OTUD3 knockdown."
37107185
OTUD3 activates cell death.
| 1
OTUD3 activates cell death. 1 / 1
| 1
reach
"Microscopic images of the cell morphology showed that OTUDin3 induced cell death in H1299 cells (Supplementary Fig. 2B)."
37369659
OTUD3 affects VEGFC
| 2
OTUD3 inhibits VEGFC. 2 / 2
| 2
reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
34853315
reach
"Wang et al. (2021) analyzed the relation between OTUD3 and lymphatic metastasis, and found that nicotine-mediated OTUD3 downregulation inhibited VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
38246894
OTUD3 affects USP25
| 2
OTUD3 binds USP25. 2 / 2
| 2
sparser
"Importantly, both OTUD3 and USP21 are present in the ribosome pellet fraction suggesting that OTUD3 and USP21 associates with ribosomes."
32011234
sparser
"Given the ability of USP21 and OTUD3 to remove RRub events, we examined if OTUD3 or USP21 associated with ribosomes."
32011234
OTUD3 affects USP13
| 2
USP11 binds USP13 and OTUD3. 1 / 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 )."
30733438
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."
32140262
OTUD3 affects TRIM25
2 |
TRIM25 binds OTUD3. 2 / 2
2 |
biogrid
No evidence text available
31266968
biogrid
No evidence text available
29117863
OTUD3 affects SIRT7
| 1 1
OTUD3 binds SIRT7. 2 / 2
| 1 1
reach
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
sparser
"At the endogenous level, we failed to validate the interaction between OTUD3 and SIRT7 (data not shown) but found that the interaction between OTUD3 and SIRT1 could be potently enhanced by SeV virus i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 affects RLR
| 2
OTUD3 inhibits RLR. 2 / 2
| 2
reach
"Interestingly, the deubiquitinating enzyme OTUD3 promotes cGAS-mediated DNA sensing but inhibits RLR-mediated RNA sensing ."
37945923
reach
"These results indicated that OTUD3 might repress RLR signaling by interfering with MAVS.To confirm this hypothesis, we performed co-immunoprecipitation assays that showed ectopically expressed OTUD3 C[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 affects Protease
| 1 1
OTUD3 binds Protease. 2 / 2
| 1 1
reach
"In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1."
38351178
sparser
"OTU deubiquitinase 3 (OTUD3) binds to the ovarian tumor-related protease family, PTEN protector."
36727069
OTUD3 affects OTUD4
1 | 1
OTUD3 binds OTUD4. 2 / 2
1 | 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
biogrid
No evidence text available
31266968
OTUD3 affects OTUB1
| 2
OTUD3 binds OTUB1. 2 / 2
| 2
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."
27066941
sparser
"OTUD3 interacts with KPTN, facilitated by the OTU domain within OTUD3."
38288086
OTUD3 affects NOS2
| 2
OTUD3 inhibits NOS2.
| 1
OTUD3 inhibits NOS2. 1 / 1
| 1
reach
"IL-6, Tnf-a, IL-1b, and Nos2, which are critical NF-kB target genes activated by MAVS aggregation, are consistently and efficiently induced by SeV in OTUD3-deficient macrophages (29)."
36531510
OTUD3 activates NOS2.
| 1
OTUD3 activates NOS2. 1 / 1
| 1
reach
"Il-6 , Tnf-α , Il-1β , and Nos2 , critical NF-κB target genes activated by MAVS aggregation, were consistently and more efficiently induced by SeV in Otud3 -deficient macrophages ( Figure 4 H)."
32679077
OTUD3 affects K63
| 2
OTUD3 binds RIGI and K63. 1 / 1
| 1
reach
"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
OTUD3 inhibits Iron Metabolism Disorders. 1 / 1
| 1
eidos
"Depletion of OTUD3 results in a disorder of iron metabolism ."
35490179
reach
"Considering that iron accumulates specifically in SN in the early stage of PD, we explored the influence of iron metabolism disorders caused by OTUD3 on neurons."
35490179
OTUD3 affects IRF3
| 2
OTUD3 leads to the phosphorylation of IRF3. 1 / 1
| 1
reach
"The reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs promoted the phosphorylation of IRF3 and IkBα in response to HSV-1 infection ( Figure 7 K)."
35675783
OTUD3-C76A leads to the phosphorylation of IRF3. 1 / 1
| 1
reach
"The reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs promoted the phosphorylation of IRF3 and IkBα in response to HSV-1 infection ( Figure 7 K)."
35675783
OTUD3 affects IKB
| 2
OTUD3 leads to the phosphorylation of IKB. 1 / 1
| 1
reach
"The reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs promoted the phosphorylation of IRF3 and IkBα in response to HSV-1 infection ( Figure 7 K)."
35675783
OTUD3-C76A leads to the phosphorylation of IKB. 1 / 1
| 1
reach
"The reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs promoted the phosphorylation of IRF3 and IkBα in response to HSV-1 infection ( Figure 7 K)."
35675783
OTUD3 affects IFIT1
| 2
OTUD3 increases the amount of IFIT1. 1 / 1
| 1
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3-C76A increases the amount of IFIT1. 1 / 1
| 1
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 inhibits DNA-templated transcription. 1 / 1
| 1
reach
"Ubiquitination assays showed that OTUD3 overexpression decreased the ubiquitination levels of these transcription regulators ( Figures 4 F–4K, lane 3 versus lane 2; Figure 4 L, lanes 2, 4, 6, 8, 10, a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD3 activates DNA-templated transcription. 1 / 1
| 1
reach
"Nuclear OTUD3, in turn, promotes glucose and fatty acid metabolism through stabilized diverse energy-metabolism-related transcription factors."
35675826
OTUD3 affects CXCL10
| 2
OTUD3 increases the amount of CXCL10. 1 / 1
| 1
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3-C76A increases the amount of CXCL10. 1 / 1
| 1
reach
"Furthermore, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs induced the transcription of the downstream genes Ifnb1 , Isg56 , Cxcl10 , and Il6 upon HSV-1 infection ( Figu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUB1 affects OTUD3
| 2
OTUD3 binds OTUB1. 2 / 2
| 2
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."
27066941
sparser
"OTUD3 interacts with KPTN, facilitated by the OTU domain within OTUD3."
38288086
KAT2A affects OTUD3
| 2
KAT2A increases the amount of OTUD3.
| 1
KAT2A increases the amount of OTUD3. 1 / 1
| 1
reach
"However, GCN5 failed to increase OTUD3 acetylation levels ( Figure S7 F, lanes 3–6 versus lanes 1 and 2)."
35675826
KAT2A acetylates OTUD3.
| 1
KAT2A leads to the acetylation of OTUD3. 1 / 1
| 1
reach
"However, GCN5 failed to increase OTUD3 acetylation levels ( Figure S7 F, lanes 3–6 versus lanes 1 and 2)."
35675826
K63 affects OTUD3
| 2
OTUD3 binds RIGI and K63. 1 / 1
| 1
reach
"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
GSK3B affects OTUD3
| 2
GSK3B phosphorylates OTUD3.
| 1
GSK3B phosphorylates OTUD3. 1 / 1
| 1
sparser
"In conclusion, GSK3β phosphorylates OTUD3, enhances its binding ability to ARID3A, and ultimately inhibits the ubiquitination degradation of ARID3A, which promotes the progression of CCA."
40181152
GSK3B binds OTUD3.
| 1
GSK3B binds OTUD3. 1 / 1
| 1
sparser
"GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
ERN1 affects OTUD3
| 2
OTUD3 binds ERN1. 2 / 2
| 2
sparser
"Our findings indicated that OTUD3 did not directly interact with IRE1α, as endogenous OTUD3 was not immunoprecipitated by IRE1α antibody in shRNA-NC and OTUD3 knockdown cells ( xref A)."
37107185
sparser
"The results showed that there was no interaction between IRE1α and OTUD3."
37107185
CD274 affects OTUD3
| 2
OTUD3 binds CD274. 2 / 2
| 2
sparser
"In HEK293T cells, His-tagged PD-L1 bound both wild-type and C76A mutant OTUD3 with Flag tags (Fig. xref ), and like MYL12A, PD-L1’s binding to wild-type OTUD3 decreased with rupatadine, indicating the C76A mutation doesn’t affect PD-L1 binding, but rupatadine can disrupt it."
39097608
sparser
"Importantly, we found that OTUD3’s interaction with PD-L1 contributes to CD8+ T cell exhaustion."
39097608
Air Pollutants affects OTUD3
2 |
Air Pollutants increases the amount of OTUD3.
1 |
Air Pollutants increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Air Pollutants decreases the amount of OTUD3.
1 |
Air Pollutants decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Volatile organic compound decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
32699268
Valproic acid affects OTUD3
1 |
Valproic acid increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
29154799
Urethane affects OTUD3
1 |
Urethane increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
28818685
Sodium arsenate affects OTUD3
1 |
Sodium arsenate decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
30953684
Resveratrol affects OTUD3
1 |
Resveratrol increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
23557933
Methylparaben affects OTUD3
1 |
Methylparaben increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
31745603
Malonaldehyde affects OTUD3
| 1
reach
"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
Hydrogen peroxide affects OTUD3
1 |
Hydrogen peroxide increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
26846883
Hsa-mir-4803 affects OTUD3
1 |
Hsa-mir-4803 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-mir-4794 affects OTUD3
1 |
Hsa-mir-4794 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-mir-4729 affects OTUD3
1 |
Hsa-mir-4729 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-mir-4457 affects OTUD3
1 |
Hsa-mir-4457 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-mir-4311 affects OTUD3
1 |
Hsa-mir-4311 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-mir-4295 affects OTUD3
1 |
Hsa-mir-4295 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-mir-3974 affects OTUD3
1 |
Hsa-mir-3974 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-mir-3672 affects OTUD3
1 |
Hsa-mir-3672 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-mir-3666 affects OTUD3
1 |
Hsa-mir-3666 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-92b-3p affects OTUD3
1 |
Hsa-miR-92b-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22473208
Hsa-miR-92a-3p affects OTUD3
1 |
Hsa-miR-92a-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22473208
Hsa-miR-769-5p affects OTUD3
1 |
Hsa-miR-769-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6864-3p affects OTUD3
1 |
Hsa-miR-6864-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6849-3p affects OTUD3
1 |
Hsa-miR-6849-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6771-3p affects OTUD3
1 |
Hsa-miR-6771-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-6770-5p affects OTUD3
1 |
Hsa-miR-6770-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-6516-3p affects OTUD3
1 |
Hsa-miR-6516-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-miR-624-3p affects OTUD3
1 |
Hsa-miR-624-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-513b-5p affects OTUD3
1 |
Hsa-miR-513b-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4786-5p affects OTUD3
1 |
Hsa-miR-4786-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4773 affects OTUD3
1 |
Hsa-miR-4773 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-4768-3p affects OTUD3
1 |
Hsa-miR-4768-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4749-3p affects OTUD3
1 |
Hsa-miR-4749-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-4671-3p affects OTUD3
1 |
Hsa-miR-4671-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-454-3p affects OTUD3
1 |
Hsa-miR-454-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-4459 affects OTUD3
1 |
Hsa-miR-4459 decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-4433a-3p affects OTUD3
1 |
Hsa-miR-4433a-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-411-3p affects OTUD3
1 |
Hsa-miR-411-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-miR-379-3p affects OTUD3
1 |
Hsa-miR-379-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-miR-32-5p affects OTUD3
1 |
Hsa-miR-32-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
22473208
Hsa-miR-301b-3p affects OTUD3
1 |
Hsa-miR-301b-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-301a-3p affects OTUD3
1 |
Hsa-miR-301a-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-216a-5p affects OTUD3
1 |
Hsa-miR-216a-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-miR-212-3p affects OTUD3
1 |
Hsa-miR-212-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-20a-3p affects OTUD3
1 |
Hsa-miR-20a-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-194-5p affects OTUD3
1 |
Hsa-miR-194-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19536157
Hsa-miR-192-5p affects OTUD3
1 |
Hsa-miR-192-5p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
19074876
Hsa-miR-132-3p affects OTUD3
1 |
Hsa-miR-132-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hsa-miR-130b-3p affects OTUD3
1 |
Hsa-miR-130b-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-130a-3p affects OTUD3
1 |
Hsa-miR-130a-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
21572407
Hsa-miR-125b-2-3p affects OTUD3
1 |
Hsa-miR-125b-2-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
23313552
Hsa-miR-1207-3p affects OTUD3
1 |
Hsa-miR-1207-3p decreases the amount of OTUD3. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
27292025
Hexabromocyclododecane increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
38995820
Helicase affects OTUD3
| 1
Helicase binds OTUD3 and CTD domains. 1 / 1
| 1
reach
"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
35675783
Glutathione-Sepharose 4B beads affects OTUD3
| 1
OTUD3 binds glutathione-Sepharose 4B beads. 1 / 1
| 1
reach
"Bacterially expressed GST and GST-OTUD3 bound to glutathione-Sepharose 4B beads (from GE) were incubated with Myc-GRP78 or Flag-OTUD3 expressed in HEK293T cells for 4 h at 4 °C in the presence of DMSO or different concentrations of Rolapitant."
38539203
Estrogen affects OTUD3
1 |
Estrogen decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
33269387
Endosulfan affects OTUD3
1 |
Endosulfan increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
29391264
Cisplatin affects OTUD3
1 |
Cisplatin decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
27594783
Chains affects OTUD3
| 1
Chains binds OTUD3. 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."
28196299
Antimony(3+) affects OTUD3
| 1
Antimony(3+) leads to the acetylation of OTUD3. 1 / 1
| 1
reach
"ACLY inhibitor SB 204990 remarkably attenuated both glucose- and FFA-stimulated OTUD3 acetylation ( Figures 6 C and S7 C, lanes 6–8 versus lanes 2–4)."
35675826
Aflatoxin B1 affects OTUD3
1 |
Aflatoxin B1 decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
33354967
Acetyl affects OTUD3
| 1
Acetyl activates OTUD3. 1 / 1
| 1
sparser
"Acetyl-activation of OTUD3 represents an unprecedented mode of protease regulation and a clear link between acetylation and Ub modification, by which the braking and accelerating system for MAVS is pr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
ZRANB1 affects OTUD3
1 |
ZRANB1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35944360
ZNF823 affects OTUD3
| 1
OTUD3 binds ZNF823. 1 / 1
| 1
reach
"The specific mechanism may be that OTUD3 directly interacts with zinc finger protein ZFP36, and stabilizes ZFP36 by inhibiting FBXW7-mediated polyubiquitination of K48 junction (Ntunzwenimana et al. 2021)."
38246894
ZNF268 affects OTUD3
1 |
OTUD3 binds ZNF268. 1 / 1
1 |
biogrid
No evidence text available
33961781
YBX1 affects OTUD3
1 |
OTUD3 binds YBX1. 1 / 1
1 |
biogrid
No evidence text available
31266968
USP13 affects USP11
| 1
USP11 binds USP13 and OTUD3. 1 / 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 )."
30733438
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."
32140262
USP11 affects USP13
| 1
USP11 binds USP13 and OTUD3. 1 / 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 )."
30733438
UBE2L3 affects OTUD3
1 |
OTUD3 binds UBE2L3. 1 / 1
1 |
biogrid
No evidence text available
23563141
UBA1 affects OTUD3
| 1
OTUD3 binds UBA1. 1 / 1
| 1
sparser
"CO-IP showed that the D3 region of IRP2 interacted with the OTU domain of OTUD3 (Fig. xref ), while D2 and D3 of IRP2 interacted with the UBA domain of OTUD3 (Fig. xref )."
35490179
Tobacco Smoke Pollution decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
33660061
TPT1 affects OTUD3
1 |
TPT1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
37107185
Silent information regulator factor 2-related enzyme 1 affects OTUD3
| 1
Silent information regulator factor 2-related enzyme 1 inhibits OTUD3. 1 / 1
| 1
reach
"Further, upon SeV infection, the Silent information regulator factor 2-related enzyme 1 (Sirt-1) deacetylates (K129) and inactivates OTUD3 and thereby prevents the K63-deubiquitinylation of MAVS [ 19 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
34016513
SRSF5 affects OTUD3
1 |
OTUD3 binds SRSF5. 1 / 1
1 |
biogrid
No evidence text available
31266968
SQSTM1 affects OTUD3
1 |
SQSTM1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
39098523
SMAD7 affects OTUD3
| 1
OTUD3 binds SMAD7. 1 / 1
| 1
sparser
"Meanwhile, endogenous OTUD3 interacted with SMAD7 in breast cancer cells (Fig.  xref F)."
40382618
SIX3 affects OTUD3
1 |
OTUD3 binds SIX3. 1 / 1
1 |
biogrid
No evidence text available
35675826
SGO1 affects OTUD3
1 |
SGO1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
Raloxifene Hydrochloride decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
33269387
RP2 affects OTUD3
1 |
OTUD3 binds RP2. 1 / 1
1 |
biogrid
No evidence text available
33961781
RNF186 affects OTUD3
| 1
RNF186 binds OTUD3. 1 / 1
| 1
sparser
"Additionally, RNF186 interacted with OTUD3 (OTU deubiquitinase 3)."
39164264
RNF112 affects OTUD3
1 |
RNF112 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
40178292
RIGI affects K63
| 1
OTUD3 binds RIGI and K63. 1 / 1
| 1
reach
"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
RELA affects OTUD3
1 |
RELA binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
33438746
Plant Extracts affects OTUD3
1 |
Plant Extracts increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
23557933
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."
32140262
PLS1 affects OTUD3
1 |
OTUD3 binds PLS1. 1 / 1
1 |
biogrid
No evidence text available
33961781
PLK1 affects PBD domain
| 1
PLK1 binds OTUD3 and PBD domain. 1 / 1
| 1
reach
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
PI3K affects OTUD3
| 1
OTUD3 binds PI3K. 1 / 1
| 1
reach
"Several studies have demonstrated that OTUD3 interacts with PTEN and induces its deubiquitination, increasing PTEN protein stability and inhibiting carcinogenic PI3K/AKT signaling (89)."
40337608
PBD domain affects PLK1
| 1
PLK1 binds OTUD3 and PBD domain. 1 / 1
| 1
reach
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
sparser
"Targeting metabolic analysis also showed that the levels of citrate, fumaric acid, succinate, and acetyl-CoA were decreased in WAT tissue of Otud3 −/− mice compared with Otud3 +/+ ( Figure S4 D), whic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD7A affects OTUD3
| 1
OTUD3 binds OTUD7A. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD6B affects OTUD3
| 1
OTUD3 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD3 affects Δ
| 1
OTUD3 activates Δ. 1 / 1
| 1
reach
"We found that deletion of OTUD3 resulted in increased intracellular reactive oxygen species (ROS), and decreased mitochondrial transmembrane potential (ΔΨm) (Fig. 2b and Supplementary Fig. 5e)."
35490179
OTUD3 affects ubiquitination
| 1
OTUD3 inhibits ubiquitination. 1 / 1
| 1
sparser
"In the presence of PTEN, ubiquitination of TOP2A is inhibited by OTUD3."
26657567
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 ."
31266968
OTUD3 affects tumorigenicity tumor metastasis
| 1
OTUD3 inhibits tumorigenicity tumor metastasis. 1 / 1
| 1
eidos
"OTUD3 suppresses tumorigenicity and tumor metastasis ."
31266968
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 ) ."
31266968
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 ) ."
31266968
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 ."
31266968
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 ."
31266968
OTUD3 affects rps3-b
| 1
OTUD3 inhibits rps3-b. 1 / 1
| 1
reach
"In this study, we reveal that OTUD3 exhibits opposing effects in the innate antiviral response to RNA and DNA viruses.Using ubiquitination assays, we found that the overexpression of OTUD3 diminished [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects rolapitant
| 1
reach
"Moreover, MST (microscale thermophoresis) assays shown that OTUD3 could directly bind to Rolapitant in vitro, but not bind well to Estradiol Cypionate (Fig. 1H)."
38539203
reach
"In addition, we discovered that the OTUD3 suppression-induced YY1 protein destabilization was proteasome-dependent and reversed by treatment with the proteasome inhibitor, MG132 (Fig. 2H, I and Supplementary Fig. S2B)."
38351178
OTUD3 affects polyubiquitin chains
| 1
OTUD3 inhibits polyubiquitin chains. 1 / 1
| 1
reach
"Because OTUD3 interacts with cGAS and its enzyme activity is required for regulating antiviral signaling, we investigated whether OTUD3 eliminated polyubiquitin chains from cGAS."
35675783
reach
"OTUD3 loss of function increases the Ub-dependent degradation of PTEN and enhances PI3K/AKT signaling in breast cancer cells ( Yuan et al., 2015 )."
35675826
OTUD3 affects mutated YY1-K4R
| 1
OTUD3 deubiquitinates mutated YY1-K4R. 1 / 1
| 1
reach
"It was revealed that OTUD3 did not deubiquitinate the mutated YY1-K4R (Fig. 3F, G)."
38351178
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 ) ."
31266968
OTUD3 affects miR-520h
| 1
MiR-520h binds OTUD3. 1 / 1
| 1
reach
"For example, miR-520h binds to OTUD3 to inhibit the expression of OTUD3 protein in breast cancer cells, which in turn enhances the resistance of breast cancer cells to paclitaxel (Geng et al., 2020)."
37829187
OTUD3 affects metabolic process
| 1
OTUD3 activates metabolic process. 1 / 1
| 1
reach
"For example, the acetyltransferase CBP promotes OTUD3 acetylation for its nuclear translocation, allowing OTUD3 to deubiquitinate and stabilize the intranuclear metabolism-associated transcription factor PPARδ thereby affecting gene expression related to glycolipid metabolism and oxidative phosphorylation (OXPHOS) (Zhou et al., 2022) (Figure 3B)."
37829187
OTUD3 affects malonaldehyde
| 1
reach
"Of note, the amount of RIG-I or MDA binding to OTUD3 significantly increased with increased vesicular stomatitis virus (VSV) infection time ( Figure S1 E) or EMCV infection time ( Figure S1 F)."
35675783
OTUD3 affects lung cancer
| 1
OTUD3 activates lung cancer. 1 / 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 ."
31266968
OTUD3 affects localization
| 1
OTUD3 activates localization. 1 / 1
| 1
reach
"OTUD3 also promotes GATOR1's lysosomal localization, a process requiring KPTN's involvement."
38288086
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 ) ."
31266968
OTUD3 affects glutathione-Sepharose 4B beads
| 1
OTUD3 binds glutathione-Sepharose 4B beads. 1 / 1
| 1
reach
"Bacterially expressed GST and GST-OTUD3 bound to glutathione-Sepharose 4B beads (from GE) were incubated with Myc-GRP78 or Flag-OTUD3 expressed in HEK293T cells for 4 h at 4 °C in the presence of DMSO or different concentrations of Rolapitant."
38539203
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)."
32011234
reach
"Nuclear OTUD3, in turn, promotes glucose and fatty acid metabolism through stabilized diverse energy-metabolism-related transcription factors."
35675826
OTUD3 activates evasion of host immune response. 1 / 1
| 1
reach
"Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1."
39097608
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 ] ."
33808506
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 ."
31266968
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 ."
33743739
OTUD3-C76A activates defense response to virus. 1 / 1
| 1
reach
"As expected, the reconstitution of Otud3 , but not Otud3 (C76A), in Otud3 -deficient MEFs promoted the cellular antiviral response, as revealed by fluorescence microscopy and flow cytometry analysis ([MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects chains
| 1
Chains binds OTUD3. 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."
28196299
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 ."
31266968
OTUD3 affects angiogenesis
| 1
OTUD3 activates angiogenesis. 1 / 1
| 1
reach
"In Bronchopulmonary dysplasia (BPD) mouse, miR-34c-5p negatively targeted OTUD3 which enhanced proliferation, angiogenesis, and migration in human pulmonary microvascular endothelial cells (HPMECs) (He et al., 2023) (Figure 3A)."
37829187
OTUD3 affects aggregation
| 1
OTUD3 inhibits aggregation. 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 ] ."
33808506
OTUD3 affects ZRANB1
1 |
ZRANB1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35944360
OTUD3 affects ZNF823
| 1
OTUD3 binds ZNF823. 1 / 1
| 1
reach
"The specific mechanism may be that OTUD3 directly interacts with zinc finger protein ZFP36, and stabilizes ZFP36 by inhibiting FBXW7-mediated polyubiquitination of K48 junction (Ntunzwenimana et al. 2021)."
38246894
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 ] ."
33292102
OTUD3 affects ZNF268
1 |
OTUD3 binds ZNF268. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects ZEP36
| 1
OTUD3 inhibits ZEP36. 1 / 1
| 1
reach
"For instance, nicotine has been shown to increase VEGF-C levels in ESCC and influence lymphatic metastasis by reducing the expression of OTUD3, thereby inhibiting the ability of ZEP36 to bind to specific regions of VEGF-C mRNA and causing its decline (77)."
37359527
OTUD3 affects YBX1
1 |
OTUD3 binds YBX1. 1 / 1
1 |
biogrid
No evidence text available
31266968
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 ."
34853315
OTUD3 affects USP11, and USP13
| 1
USP11 binds USP13 and OTUD3. 1 / 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 )."
30733438
OTUD3 affects UBE2L3
1 |
OTUD3 binds UBE2L3. 1 / 1
1 |
biogrid
No evidence text available
23563141
OTUD3 affects UBA1
| 1
OTUD3 binds UBA1. 1 / 1
| 1
sparser
"CO-IP showed that the D3 region of IRP2 interacted with the OTU domain of OTUD3 (Fig. xref ), while D2 and D3 of IRP2 interacted with the UBA domain of OTUD3 (Fig. xref )."
35490179
OTUD3 affects Tnf-α
| 1
OTUD3 activates Tnf-α. 1 / 1
| 1
reach
"Il-6 , Tnf-α , Il-1β , and Nos2 , critical NF-κB target genes activated by MAVS aggregation, were consistently and more efficiently induced by SeV in Otud3 -deficient macrophages ( Figure 4 H)."
32679077
reach
"OTUD3 is a member of the OTU family that participates in the regulation of multiple physiological processes, and the aberrant expression of OTUD3 triggers tumorigenesis in esophageal cancer, breast cancer and papillary thyroid carcinoma (87,88)."
40337608
OTUD3 affects TNF
| 1
OTUD3 inhibits TNF. 1 / 1
| 1
reach
"IL-6, Tnf-a, IL-1b, and Nos2, which are critical NF-kB target genes activated by MAVS aggregation, are consistently and efficiently induced by SeV in OTUD3-deficient macrophages (29)."
36531510
OTUD3 affects SRSF5
1 |
OTUD3 binds SRSF5. 1 / 1
1 |
biogrid
No evidence text available
31266968
OTUD3 affects SQSTM1
1 |
SQSTM1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
39098523
OTUD3 affects SMAD7
| 1
OTUD3 binds SMAD7. 1 / 1
| 1
sparser
"Meanwhile, endogenous OTUD3 interacted with SMAD7 in breast cancer cells (Fig.  xref F)."
40382618
OTUD3 affects SIX3
1 |
OTUD3 binds SIX3. 1 / 1
1 |
biogrid
No evidence text available
35675826
OTUD3 affects SGO1
1 |
SGO1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 affects S2B
| 1
OTUD3 inhibits S2B. 1 / 1
| 1
reach
"Additionally, knockdown of OTUD3 in HFF cells enhanced SeV- and EMCV-induced IFNB1 and IL6 expression, whereas the ectopic expression of OTUD3 suppressed the SeV- and EMCV-induced IFNB1 and IL6 expres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects RRub
| 1
OTUD3 deubiquitinates RRub on S40. 1 / 1
| 1
reach
"OTUD3 and USP21 deubiquitylate 40S ribosomal proteins following RRub induction."
32011234
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."
32011234
OTUD3 affects RP2
1 |
OTUD3 binds RP2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects RNF186
| 1
RNF186 binds OTUD3. 1 / 1
| 1
sparser
"Additionally, RNF186 interacted with OTUD3 (OTU deubiquitinase 3)."
39164264
OTUD3 affects RNF112
1 |
RNF112 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
40178292
OTUD3 affects RELA
1 |
RELA binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
33438746
OTUD3 affects Proteasome
| 1
OTUD3 inhibits Proteasome. 1 / 1
| 1
reach
"In addition, we discovered that the OTUD3 suppression-induced YY1 protein destabilization was proteasome-dependent and reversed by treatment with the proteasome inhibitor, MG132 (Fig. 2H, I and Supplementary Fig. S2B)."
38351178
OTUD3 affects Parkinson’s
| 1
OTUD3 inhibits Parkinson’s. 1 / 1
| 1
reach
"The deubiquitinase OTUD3 prevents Parkinson’s disease by stabilizing IRP2 [17]."
39415292
OTUD3 affects Parkinson’s disease
| 1
OTUD3 inhibits Parkinson’s disease. 1 / 1
| 1
reach
"In addition, OTUD3 prevented Parkinson’s disease (PD) by stabilizing iron regulatory protein 2 [28]."
37369659
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."
32140262
OTUD3 affects PPAR
| 1
OTUD3 decreases the amount of PPAR. 1 / 1
| 1
reach
"Consistent with this finding, knockdown of Otud3 in HEK293T cells showed increased ubiquitination levels of PPARδ ( Figure S6 D, lanes 2 and 3 versus lane 1), and exogenous expression of WT OTUD3, but[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD3 affects PLS1
1 |
OTUD3 binds PLS1. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects PEPD
| 1
OTUD3 activates PEPD. 1 / 1
| 1
reach
"OTUD3 depletion by shRNA obviously potentiated the SeV-induced activity of the Ifnb1 promoter and the positive regulatory domain (PRD) I–III reporter, which contained an IRF3-binding site ( Figures S1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32679077
OTUD3 affects PBD domain, and PLK1
| 1
PLK1 binds OTUD3 and PBD domain. 1 / 1
| 1
reach
"In this study, we found that the PBD domain of PLK1 binds OTUD3."
38351178
sparser
"Targeting metabolic analysis also showed that the levels of citrate, fumaric acid, succinate, and acetyl-CoA were decreased in WAT tissue of Otud3 −/− mice compared with Otud3 +/+ ( Figure S4 D), whic[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD3 affects Obesity
| 1
OTUD3 activates Obesity. 1 / 1
| 1
reach
"Taken together, Otud3 −/− mice are predisposed to obesity and develop worse glucose intolerance, insulin resistance, and dyslipidemia after metabolic challenge.To explore why Otud3 −/− mice are suscep[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
OTUD3 affects OTUD7A
| 1
OTUD3 binds OTUD7A. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD3 affects OTUD6B
| 1
OTUD3 binds OTUD6B. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD3 affects OTUD3-GRP78
| 1
OTUD3 inhibits OTUD3-GRP78. 1 / 1
| 1
reach
"Based on these findings, we concluded that OTUDin3 inhibits NSCLC by targeting the OTUD3-GRP78 signaling axis (Fig. 6)."
37369659
OTUD3 inhibits N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal. 1 / 1
| 1
reach
"In addition, we discovered that the OTUD3 suppression-induced YY1 protein destabilization was proteasome-dependent and reversed by treatment with the proteasome inhibitor, MG132 (Fig. 2H, I and Supplementary Fig. S2B)."
38351178
OTUD3 affects MYH9
1 |
OTUD3 binds MYH9. 1 / 1
1 |
biogrid
No evidence text available
31266968
OTUD3 affects MTOR
| 1
OTUD3 inhibits MTOR. 1 / 1
| 1
reach
"3.7 OTUD3 suppressed proliferation and growth of HeLa by downregulating mTOR signaling mediated cell metabolism."
38288086
OTUD3 affects MIB1
1 |
OTUD3 binds MIB1. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects Lys279
| 1
OTUD3 binds CGAS and Lys279. 1 / 1
| 1
reach
"OTUD3 binds cGAS and targets the Lys279 site for deubiquitination of k48- and k27-linked ubiquitination, thereby enhancing cGAS protein stability and DNA binding capacity (Cai et al., 2022)."
37829187
OTUD3 inhibits Lymphatic Metastasis. 1 / 1
| 1
reach
"Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer."
34853315
OTUD3 affects Leukemia
| 1
OTUD3 activates Leukemia. 1 / 1
| 1
reach
"These results suggested that OTUD3 may promote tumorigenesis in leukemia."
34815255
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)."
33931739
OTUD3 affects KPRP
1 |
OTUD3 binds KPRP. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects KICSTOR
| 1
OTUD3 binds KICSTOR. 1 / 1
| 1
reach
"It remains uncertain whether all these interactions between OTUD3 and KICSTOR have biological significance and whether all the KICSTOR components substrates of OTUD3’s deubiquitination activity."
38288086
OTUD3 affects KBTBD7
1 |
OTUD3 binds KBTBD7. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects KAT6A
1 |
KAT6A binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
33995658
OTUD3 affects K6-, K11-, K27-, K29-, K33-,
| 1
OTUD3 leads to the deubiquitination of K6-, K11-, K27-, K29-, K33-, on K48. 1 / 1
| 1
reach
"As expected, overexpression of OTUD3 decreased K63-linked polyubiquitination of RIG-I and MDA5 ( Figures 2 A and 2B ), but not K6-, K11-, K27-, K29-, K33-, and K48-linked polyubiquitination ( Figures [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects Il-1β
| 1
OTUD3 activates Il-1β. 1 / 1
| 1
reach
"Il-6 , Tnf-α , Il-1β , and Nos2 , critical NF-κB target genes activated by MAVS aggregation, were consistently and more efficiently induced by SeV in Otud3 -deficient macrophages ( Figure 4 H)."
32679077
OTUD3 affects ITFG2
1 |
OTUD3 binds ITFG2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects ISRE luciferase reporter
| 1
OTUD3 activates ISRE luciferase reporter. 1 / 1
| 1
reach
"Overexpression of OTUD3 was found to enhance the STING/cGAS combination-induced activation of ISRE luciferase reporter and IFN-β promoter luciferase reporter, but not STING alone-induced activation of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects ISR
| 1
OTUD3 inhibits ISR. 1 / 1
| 1
reach
"OTUD3 deficiency in mice leads to enhanced ISR and accelerated progression of N-nitrosodiethylamine-induced hepatocellular carcinoma."
38996071
OTUD3 affects IRS4
1 |
OTUD3 binds IRS4. 1 / 1
1 |
biogrid
No evidence text available
31266968
OTUD3 affects INTS12
1 |
OTUD3 binds INTS12. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 affects IL1B
| 1
OTUD3 inhibits IL1B. 1 / 1
| 1
reach
"IL-6, Tnf-a, IL-1b, and Nos2, which are critical NF-kB target genes activated by MAVS aggregation, are consistently and efficiently induced by SeV in OTUD3-deficient macrophages (29)."
36531510
OTUD3 affects HSD17B14
1 |
HSD17B14 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
32296183
OTUD3 affects HRAS
1 |
OTUD3 binds HRAS. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects HOXB8
1 |
OTUD3 binds HOXB8. 1 / 1
1 |
biogrid
No evidence text available
35675826
OTUD3 affects HMOX1
| 1
OTUD3 increases the amount of HMOX1. 1 / 1
| 1
reach
"Immunoblotting results showed that the knockdown of OTUD3 in A549 cells with erastin decreased the expression of GPX4, HO-1, and xCT (Fig. 5H)."
39043653
OTUD3 affects GTF2A1
| 1
GTF2A1 binds OTUD3. 1 / 1
| 1
sparser
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [ xref ]."
38841185
OTUD3 affects GSK3B
| 1
GSK3B binds OTUD3. 1 / 1
| 1
sparser
"GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
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 ) ."
31266968
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 ."
32483383
OTUD3 affects GPX4
| 1
OTUD3 increases the amount of GPX4. 1 / 1
| 1
reach
"Immunoblotting results showed that the knockdown of OTUD3 in A549 cells with erastin decreased the expression of GPX4, HO-1, and xCT (Fig. 5H)."
39043653
OTUD3 affects GNG10
1 |
OTUD3 binds GNG10. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects GNB2
1 |
OTUD3 binds GNB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects GNAT3
1 |
OTUD3 binds GNAT3. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects GNA13
1 |
OTUD3 binds GNA13. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects GNA11
1 |
OTUD3 binds GNA11. 1 / 1
1 |
biogrid
No evidence text available
33961781
OTUD3 affects FOXN1
1 |
OTUD3 binds FOXN1. 1 / 1
1 |
biogrid
No evidence text available
35675826
OTUD3 affects FOXA2
1 |
OTUD3 binds FOXA2. 1 / 1
1 |
biogrid
No evidence text available
35675826
OTUD3 affects FLII
1 |
FLII binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
34060252
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))."
34060252
OTUD3 affects FBN2
| 1
OTUD3 activates FBN2. 1 / 1
| 1
reach
"OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
OTUD3 affects DHX9
1 |
OTUD3 binds DHX9. 1 / 1
1 |
biogrid
No evidence text available
31266968
OTUD3 affects DGKA
1 |
DGKA binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 activates Cholangiocarcinoma. 1 / 1
| 1
reach
"Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma."
40181152
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)."
32011234
OTUD3 inhibits Carcinoma, Squamous Cell. 1 / 1
| 1
reach
"Lower expression in gliomas suggests involvement in gliomagenesis, while OTUD3 locus deletion may contribute to squamous cell carcinoma (Liu et al., 2020; Gatti et al., 2020)."
38288086
reach
"OTUD3 deficiency in mice leads to enhanced ISR and accelerated progression of N-nitrosodiethylamine-induced hepatocellular carcinoma."
38996071
OTUD3 affects CTTN
1 |
CTTN binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 affects CTD domains
| 1
Helicase binds OTUD3 and CTD domains. 1 / 1
| 1
reach
"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
35675783
OTUD3 affects CS
| 1
CS binds OTUD3. 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)."
32011234
OTUD3 affects CARD
| 1
OTUD3 leads to the deubiquitination of CARD. 1 / 1
| 1
reach
"We further confirmed that overexpression of OTUD3 reduced K63-linked polyubiquitination of CARD and helicase domains of RIG-I and MDA5 ( Figures S3 C–S3F), implying that the deubiquitination of RIG-I [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
OTUD3 affects CADPS2
1 |
OTUD3 binds CADPS2. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 affects BP
| 1
OTUD3 binds BP. 1 / 1
| 1
sparser
"By using 90-bp dsDNA in DNA shift assay ( Figures 6 C and 6D), we further established that the Kd (equilibrium dissociation constant) of 90-bp dsDNA binding to OTUD3 is about 0.5 μM. To examine whethe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
OTUD3 affects BHLHE22
1 |
OTUD3 binds BHLHE22. 1 / 1
1 |
biogrid
No evidence text available
35675826
OTUD3 activates Adenocarcinoma of Lung. 1 / 1
| 1
reach
"Mechanistically, OTUD3 promotes the proliferation of lung adenocarcinoma through deubiquitylation and stabilization of GRP78 [2]."
38539203
OTUD3 affects AURKA
1 |
OTUD3 binds AURKA. 1 / 1
1 |
biogrid
No evidence text available
33669244
OTUD3 affects ATG14
1 |
OTUD3 binds ATG14. 1 / 1
1 |
biogrid
No evidence text available
37632749
OTUD3 affects AGO2
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AGO2 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
18461144
OTUD3 affects ADAP1
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ADAP1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
OTUD3 CS affects OTUD3
| 1
Mutated OTUD3 CS decreases the amount of OTUD3. 1 / 1
| 1
reach
"Consistent with the inhibitory effects of OTUD3 on MAVS ubiquitination, we found the aggregation of MAVS to be suppressed by ectopic expression of OTUD3-WT and not by OTUD3 CS mutant ( Figure 4 D)."
32679077
OTU affects OTUD3
| 1
OTU deubiquitinates OTUD3. 1 / 1
| 1
reach
"Very recently, ovarian tumor protease (OTU) deubiquitinating enzyme 3 (OTUD3), a deubiquitination enzyme, was reported to bind to MDA5 and RIG-I and ultimately remove their Lys-63-linked polyubiquitination to diminish the signal transduction of RLRs, thus inhibiting the antiviral immune response against RNA viruses (Figure 2) [108]."
36980296
Neoplasms affects OTUD3
| 1
Neoplasms activates OTUD3. 1 / 1
| 1
reach
"To determine whether OTUD3 promotes tumor progression by regulating YY1, we restored the expression of YY1 in endogenous OTUD3 depletion CRC cells or knocked down endogenous YY1 in OTUD3-overexpressing CRC cells."
38351178
Nanotubes, Carbon affects OTUD3
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Nanotubes, Carbon increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
25554681
NFE2L2 affects BUB1B
| 1
BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
reach
"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
Myc-PLK1 protein affects OTUD3
| 1
Myc-PLK1 protein phosphorylates OTUD3. 1 / 1
| 1
reach
"In vitro kinase assays showed that OTUD3 protein was phosphorylated by Myc-PLK1 protein that were purified from HEK-293T cells (Fig. 5H)."
38351178
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."
37310728
MiR-520h affects OTUD3
| 1
MiR-520h bound to region decreases the amount of OTUD3. 1 / 1
| 1
reach
"MiR-520h binds to the 3′-untranslated region (3′-UTR) of OTUD3 and inhibits OTUD3 protein expression, which in turn inhibits PTEN expression and ultimately activates the downstream pathway AKT."
37829187
MiR-32 affects OTUD3
| 1
MiR-32 decreases the amount of OTUD3. 1 / 1
| 1
reach
"MiR-32 also inhibits the expression of OTUD3 and promotes cell proliferation and motility and inhibits apoptosis in colon cancer cells (Jin et al., 2019)."
37829187
MYH9 affects OTUD3
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OTUD3 binds MYH9. 1 / 1
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biogrid
No evidence text available
31266968
MIB1 affects OTUD3
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OTUD3 binds MIB1. 1 / 1
1 |
biogrid
No evidence text available
33961781
MAVS affects K63
| 1
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
Lys279 affects OTUD3
| 1
OTUD3 binds CGAS and Lys279. 1 / 1
| 1
reach
"OTUD3 binds cGAS and targets the Lys279 site for deubiquitination of k48- and k27-linked ubiquitination, thereby enhancing cGAS protein stability and DNA binding capacity (Cai et al., 2022)."
37829187
Lung Injury affects OTUD3
| 1
Lung Injury 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."
37310728
KPRP affects OTUD3
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OTUD3 binds KPRP. 1 / 1
1 |
biogrid
No evidence text available
33961781
KICSTOR affects OTUD3
| 1
OTUD3 binds KICSTOR. 1 / 1
| 1
reach
"It remains uncertain whether all these interactions between OTUD3 and KICSTOR have biological significance and whether all the KICSTOR components substrates of OTUD3’s deubiquitination activity."
38288086
KBTBD7 affects OTUD3
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OTUD3 binds KBTBD7. 1 / 1
1 |
biogrid
No evidence text available
33961781
KAT6A affects OTUD3
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KAT6A binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
33995658
K63 affects RIGI
| 1
OTUD3 binds RIGI and K63. 1 / 1
| 1
reach
"In contrast, the deubiquitinase OTUD3 binds to RIG-I/MDA5 and removes K63-linked ubiquitination, leading to reduced binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS [68]."
36755342
K63 affects MAVS, and OTUD3
| 1
OTUD3 binds MAVS and K63. 1 / 1
| 1
reach
"Studies have found that OTUD3 can directly bind to MAVS and remove its K63-linked ubiquitin chains to turn off the antiviral signal (135)."
36505476
Interferon affects OTUD3
| 1
Interferon decreases the amount of OTUD3. 1 / 1
| 1
reach
"Interferon induces downregulation of CYLD to promote RIG-I K63-linked ubiquitination for its activation (132) and reduces OTUD3 expression to allow MAVS to undergo K63-linked ubiquitination and activation (158)."
35795661
Infections affects OTUD3
| 1
Infections leads to the deacetylation of OTUD3 on K129. 1 / 1
| 1
reach
"SeV infection reduced Lys129 acetylation of OTUD3 in control cells, but not in cells depleted with SIRT1 ( Figure 6 G), indicating that endogenous SIRT1 is required."
32679077
ITFG2 affects OTUD3
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OTUD3 binds ITFG2. 1 / 1
1 |
biogrid
No evidence text available
33961781
IRS4 affects OTUD3
1 |
OTUD3 binds IRS4. 1 / 1
1 |
biogrid
No evidence text available
31266968
IRE1alpha inhibitor affects OTUD3
| 1
IRE1alpha inhibitor activates OTUD3. 1 / 1
| 1
reach
"The ratio of p-IRE1alpha/IRE1alpha, and the expression of X-box binding protein 1-spliced (XBP1s) were remarkably increased after OTUD3 knockdown, which was inhibited by IRE1alpha inhibitor STF-083010 treatment."
37107185
INTS12 affects OTUD3
1 |
OTUD3 binds INTS12. 1 / 1
1 |
biogrid
No evidence text available
35575683
Hyperoxia affects OTUD3
| 1
Hyperoxia 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."
37310728
HSD17B14 affects OTUD3
1 |
HSD17B14 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
32296183
HRAS affects OTUD3
1 |
OTUD3 binds HRAS. 1 / 1
1 |
biogrid
No evidence text available
33961781
HOXB8 affects OTUD3
1 |
OTUD3 binds HOXB8. 1 / 1
1 |
biogrid
No evidence text available
35675826
HMN-214 affects OTUD3
| 1
HMN-214 leads to the dephosphorylation of OTUD3. 1 / 1
| 1
reach
"Pretreatment with the PLK1-specific inhibitor, HMN-214 (3 μM, 6 h), significantly inhibited OTUD3 phosphorylation (Fig. 5I and Supplementary Fig. S4K–L)."
38351178
G_protein affects OTUD3
| 1
G_protein activates OTUD3. 1 / 1
| 1
reach
"Moreover, the transcription of N and G protein genes of SVCV significantly increased in otud3 −/− embryos injected with WT otud3 compared with otud3 −/− embryos injected with otud3 (C70A) or GFP mRNA [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675783
GTF2A1 affects OTUD3
| 1
GTF2A1 binds OTUD3. 1 / 1
| 1
sparser
"Besides, CHIP interacts with OTU deubiquitinase 3 (OTUD3) and induces polyubiquitination and degradation of OTU3, thereby inhibiting OTUD3-glucose regulated protein 78 (GRP78) signaling, and impairing invasion and metastasis in NSCLC [ xref ]."
38841185
GSK3 affects OTUD3
| 1
GSK3 phosphorylates OTUD3. 1 / 1
| 1
reach
"In conclusion, GSK3β phosphorylates OTUD3, enhances its binding ability to ARID3A, and ultimately inhibits the ubiquitination degradation of ARID3A, which promotes the progression of CCA."
40181152
GSK-J4 affects OTUD3
1 |
GSK-J4 increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
29301935
GNG10 affects OTUD3
1 |
OTUD3 binds GNG10. 1 / 1
1 |
biogrid
No evidence text available
33961781
GNB2 affects OTUD3
1 |
OTUD3 binds GNB2. 1 / 1
1 |
biogrid
No evidence text available
33961781
GNAT3 affects OTUD3
1 |
OTUD3 binds GNAT3. 1 / 1
1 |
biogrid
No evidence text available
33961781
GNA13 affects OTUD3
1 |
OTUD3 binds GNA13. 1 / 1
1 |
biogrid
No evidence text available
33961781
GNA11 affects OTUD3
1 |
OTUD3 binds GNA11. 1 / 1
1 |
biogrid
No evidence text available
33961781
Flame Retardants affects OTUD3
1 |
Flame Retardants increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
38995820
FR900359 affects OTUD3
1 |
FR900359 phosphorylates OTUD3. 1 / 1
1 |
ctd
No evidence text available
37730182
FOXN1 affects OTUD3
1 |
OTUD3 binds FOXN1. 1 / 1
1 |
biogrid
No evidence text available
35675826
FOXA2 affects OTUD3
1 |
OTUD3 binds FOXA2. 1 / 1
1 |
biogrid
No evidence text available
35675826
FLII affects OTUD3
1 |
FLII binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
34060252
FFAR2 affects OTUD3
| 1
FFAR2 acetylates OTUD3. 1 / 1
| 1
sparser
"ACLY inhibitor SB 204990 remarkably attenuated both glucose- and FFA-stimulated OTUD3 acetylation ( Figures 6 C and S7 C, lanes 6–8 versus lanes 2–4)."
35675826
Deubiquitinase affects OTUD3
| 1
Deubiquitinase activates OTUD3. 1 / 1
| 1
reach
"The G288D mutant with impaired DUB activity may potentially compete with WT OTUD3 for substrates and decreases the efficiency of WT OTUD3, which also meets the definition of dominant negative ( Veitia[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
35675826
DHX9 affects OTUD3
1 |
OTUD3 binds DHX9. 1 / 1
1 |
biogrid
No evidence text available
31266968
DGKA affects OTUD3
1 |
DGKA binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
CTTN affects OTUD3
1 |
CTTN binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
CTD domains affects helicase
| 1
Helicase binds OTUD3 and CTD domains. 1 / 1
| 1
reach
"Domain mapping showed that the OTU domain (1–183 amino acids [aa]) of OTUD3 binds to RIG-I or MDA5, and all 2CARD, helicase, and CTD domains of RIG-I and MDA5 bind to OTUD3 ( Figures S1 H and S1I)."
35675783
CS affects OTUD3
| 1
CS binds OTUD3. 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)."
32011234
CGAS affects Lys279, and OTUD3
| 1
OTUD3 binds CGAS and Lys279. 1 / 1
| 1
reach
"OTUD3 binds cGAS and targets the Lys279 site for deubiquitination of k48- and k27-linked ubiquitination, thereby enhancing cGAS protein stability and DNA binding capacity (Cai et al., 2022)."
37829187
CADPS2 affects OTUD3
1 |
OTUD3 binds CADPS2. 1 / 1
1 |
biogrid
No evidence text available
35575683
BUB1B affects NFE2L2, and OTUD3
| 1
BUB1B binds NFE2L2 and OTUD3. 1 / 1
| 1
reach
"The BUB1b-NRF2-OTUD3 complex enhances the NRF2 signaling pathway, which suppresses ferroptosis and induces chemoresistance."
39043653
BP affects OTUD3
| 1
OTUD3 binds BP. 1 / 1
| 1
sparser
"By using 90-bp dsDNA in DNA shift assay ( Figures 6 C and 6D), we further established that the Kd (equilibrium dissociation constant) of 90-bp dsDNA binding to OTUD3 is about 0.5 μM. To examine whethe[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36966392
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."
37310728
BHLHE22 affects OTUD3
1 |
OTUD3 binds BHLHE22. 1 / 1
1 |
biogrid
No evidence text available
35675826
AURKA affects OTUD3
1 |
OTUD3 binds AURKA. 1 / 1
1 |
biogrid
No evidence text available
33669244
ATG14 affects OTUD3
1 |
OTUD3 binds ATG14. 1 / 1
1 |
biogrid
No evidence text available
37632749
ARID3A.GSK3β affects OTUD3
| 1
ARID3A.GSK3β leads to the phosphorylation of OTUD3 on S9. 1 / 1
| 1
reach
"OTUD3 promotes CCA proliferation and metastasis in vivo and in vitro by interacting with ARID3A.GSK3β interacts with OTUD3 protein and mediates phosphorylation of the Ser9 site of OTUD3, which enhances the affinity of OTUD3 to ARID3A and further stabilizes ARID3A protein."
40181152
ARID3A affects OTUD3
| 1
ARID3A binds OTUD3. 1 / 1
| 1
sparser
"A well-characterized example involves GSK3β-mediated phosphorylation at Ser9, which promotes OTUD3 binding to the transcription factor ARID3A. This interaction facilitates ARID3A deubiquitination and stabilization, driving proliferation and metastasis in cholangiocarcinoma (CCA)."
41437362
AGO2 affects OTUD3
1 |
AGO2 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
18461144
ADAP1 affects OTUD3
1 |
ADAP1 binds OTUD3. 1 / 1
1 |
biogrid
No evidence text available
35575683
ACLY inhibitor affects OTUD3
| 1
ACLY inhibitor leads to the acetylation of OTUD3. 1 / 1
| 1
reach
"ACLY inhibitor SB 204990 remarkably attenuated both glucose- and FFA-stimulated OTUD3 acetylation ( Figures 6 C and S7 C, lanes 6–8 versus lanes 2–4)."
35675826
6-propyl-2-thiouracil decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
24780913
ctd
No evidence text available
39298647
3-(4-dimethylaminobenzylidene)-1,3-dihydroindol-2-one decreases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
39786591
2,3,7,8-tetrachlorodibenzodioxine increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
21296121
17alpha-ethynylestradiol increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
23129252
2,2',4,4'-tetrabromodiphenyl ether increases the amount of OTUD3. 1 / 1
1 |
ctd
No evidence text available
38995820