IndraLab
Statements
OTUB1 is modified
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OTUB1 is phosphorylated.
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"CK2-mediated phosphorylation of OTUB1 at S16 acts as a molecular switch that drives nuclear accumulation, which is essential for repairing ionizing radiation-induced DNA damage, independent of changes to its intrinsic catalytic activity. xref This phosphorylation pathway can be activated by cathepsin K inhibition (e.g., with odanacatib), leading to enhanced p53 stabilization and apoptosis sensitization. xref Conversely, phosphorylation at tyrosine 26 (Y26) by non-receptor tyrosine kinases (e.g., Src) induces distinct conformational changes that promote the specific stabilization of the mTORC1 component Raptor without affecting other substrates, demonstrating the high specificity of phosphorylation-mediated regulation. xref Additionally, the phosphorylated Y26 residue serves as a docking site for the cell cycle regulator p27, connecting OTUB1 to IFNγ-induced cell-cycle arrest. xref These mechanisms demonstrate how site-specific phosphorylation enables OTUB1 to process disparate upstream signals, such as DNA damage, and direct appropriate downstream responses."
OTUB1 is phosphorylated on S16. 4 / 4
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OTUB1 is hydroxylated.
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"Next, we analyzed whether IκBβ is hydroxylated by FIH via mass spectrometry (MS), because for OTUB1 the same asparagine residue that is involved in oxomer formation is also hydroxylated in monomeric OTUB1. xref We identified IκBß peptides containing four of the five asparagine residues."
sparser
"In order to investigate if the observed OTUB1 N22 hydroxylation was regulated by physiologically relevant changes in the cellular microenvironment, we incubated HEK293 cells overexpressing both OTUB1 and FIH in 0.2% oxygen for 8 h with and without subsequent re-oxygenation at 21% oxygen for one additional hour."
OTUB1 is methylated.
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"Moreover, SETD7, a lysine monomethylase, directly interacts with OTUB1 to catalyze the methylation of OTUB1 at Lys 122, disrupting the interaction between OTUB1 and the anti -ferroptosis protein ubiquitin conjugating enzyme E2 N (UBE2N/UBC13) in H1299 lung cancer cells [ xref ]."
sparser
"SETD7, a lysine monomethylase, directly interacts with ubiquitin thioesterase 1 (OTUB1) to catalyse OTUB1 methylation at Lys 122, disrupting the interaction between OTUB1 and the anti-ferroptosis protein ubiquitin conjugating enzyme E2 N (UBE2N/UBC13) in H1299 lung cancer cells xref ."
OTUB1 is dephosphorylated.
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"Moreover, inhibition of cathepsin K (by ODN and siRNA) significantly increased SHP2 phosphorylation at Y542, and SHP2 inhibition (by using pharmacological inhibitor and siRNA) interrupted the ODN-mediated dephosphorylation of OTUB1 and Src, eventually stabilizing Raptor (Fig. 2C–F)."
sparser
"Moreover, inhibition of cathepsin K (by ODN and siRNA) significantly increased SHP2 phosphorylation at Y542, and SHP2 inhibition (by using pharmacological inhibitor and siRNA) interrupted the ODN-mediated dephosphorylation of OTUB1 and Src, eventually stabilizing Raptor (Fig. xref )."
OTUB1 is ubiquitinated.
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"Another study revealed that circIGF2BP3 functioned as the molecular sponge of miR-328-3p and miR-3173-5p to upregulate plakophilin 3 (PKP3) expression, thereby increasing ovarian tumor (OTU) family deubiquitinase ubiquitin aldehyde binding 1 (OTUB1) level and facilitating PD-L1 deubiquitination [8]."
sparser
"As m6A eraser, FTO mainly plays demethylation activity for the m6A of single‐stranded RNA, thus regulating gene expression. xref , xref Huang et al. xref revealed that FTO suppressed nasopharyngeal carcinoma cell ferroptosis to enhance radioresistance via stabilizing the interaction between OTUB1 and SLC7A11 by inhibiting the m6A modification of OTUB1."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
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"84
Liang et al.
85
found that SM inhibited the transcriptional regulation of Transcription factor activating enhancer binding protein 2 alpha (TFAP2A) to OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in human pancreatic cancer cells (PANC‐1 and CFPAC‐1), which in turn inhibited the deubiquitination of SLC7A11 proteins by OTUB1, induced SLC7A11 degradation, activating iron death and inhibiting pancreatic cancer cell progression.3.5
Colorectal cancer."
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"Consistent with the role of a DUB in regulating protein stability, OTUB1 overexpression resulted in reduced SLC7A11 ubiquitination and increased SLC7A11 protein half-life and steady protein levels; conversely, OTUB1 deletion in a variety of cancer cell lines resulted in a significant decrease in SLC7A11 protein levels."
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"Taken together, although the precise mechanism by which OTUB1 induces SLC7A11 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and SLC7A11 as well as OTUB1 's ability of inhibiting E2 conjugating enzymes recruited by the unknown E3 ligase contribute to SLC7A11 stabilization induced by OTUB1."
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"For example, in a non neuronal setting, induction of ferroptosis with the small molecule erastin is suppressed by the ubiquitin ligase NEDD4 [XREF_BIBR], whilst the DUBs OTUB1 and USP7 promote ferroptosis by stabilising the mediators SLC7A11 and p53, respectively [XREF_BIBR, XREF_BIBR]."
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"In light of the latter findings, future studies addressing whether conditions of diminished GSH levels or increased GSH oxidation affect deubiquitinase S-glutathionylation and implications for their canonical or alternative functions, therefore, appears well warranted.The OTUB1-mediated stabilization of SLC7A11 following its S-glutathionylation depicts a regulatory feed forward mechanism whereby GSH, in a form of a protein-mixed disulfide with OTUB1, regulates its own synthesis in an SLC7A11-dependent manner."
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"In particular, our results show that (i) OTUB1 is a bona fide binding partner of SLC7A11 both in vitro and in vivo; (ii) OTUB1 acts as a major regulator for SLC7A11 activity in human cancer cells; (iii) OTUB1 inactivation promotes ferroptosis in human cancer cells primarily by down-regulating SLC7A11 levels; (iv) OTUB1 is overexpressed in human cancers and the OTUB1-SLC7A11 interaction is critical for tumor growth; (v) The OTUB1-SLC7A11 interaction is tightly regulated by CD44 in human cancer cells."
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"Although human ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1) was previously identified as a K48 linkage specific deubiquitinating enzyme that positively regulates p53 stability 22, OTUB1 strongly suppresses E2-ubiquitin-conjugating enzyme UBC13 dependent K63 linked ubiquitination XREF_BIBR, XREF_BIBR."
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"Other cellular regulators of Ubc13/UBE2N have been described, notably the OTUB family proteins, A20 (TNFΑIP3) and OTUB1, which can inactivate Ubc13/UBE2N signaling to NF-κB from TRAF, TLR, IL-1β, TNFα, and DNA repair pathways (Nakada et al., 2010; Shembade and Harhaj, 2010; Shembade et al., 2010)."
sparser
"As m6A eraser, FTO mainly plays demethylation activity for the m6A of single‐stranded RNA, thus regulating gene expression. xref , xref Huang et al. xref revealed that FTO suppressed nasopharyngeal carcinoma cell ferroptosis to enhance radioresistance via stabilizing the interaction between OTUB1 and SLC7A11 by inhibiting the m6A modification of OTUB1."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
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"Taking together, our present study revealed that OTUB1 played a crucial role in the development of pancreatic cancer, and NDUFS2, identified as a substrate of OTUB1, might be responsible for the observed phenotypes in the absence of OTUB1 in pancreatic cancer.A recent report showed that OTUB1 may accelerate metastasis of pancreatic cancer by inhibiting FOXM1 degradation [20]."
OTUB1 affects Genome polyprotein
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OTUB1 binds Genome polyprotein.
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OTUB1 binds Genome polyprotein. 10 / 61
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"During non‐canonical deubiquitination, OTUB1 preferentially binds to ubiquitin‐conjugated E2, which restricts ubiquitin transfer. [ xref ] Moreover, the binding surface of OTUB1/E2 interferes with the interaction between E2 and E3, which further inhibits ubiquitination. [ xref ] "
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"Together, the inhibitory profile of the OTUB1 mutants was fully consistent with the crystal structure of the Ub ~ E2 and OTUB1-Ub complex and demonstrated (1) that the E2 interaction surface on OTUB1, remote from its catalytic site, was dispensable for its DUB function, and (2) that both Ub interaction surfaces on OTUB1 were required for its isopeptidase activity, as they likely engage K48 linked di-Ub substrates."
OTUB1 inhibits Genome polyprotein.
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OTUB1 inhibits Genome polyprotein. 10 / 40
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"Resulting changes in substrate ubiquitination or downstream signaling pathways in cells expressing the mutant DUB are generally assumed to be due to the absence of deubiquitinating activity, with the notable exceptions of OTUB1, which inhibits E2 enzymes by a mechanism independent of catalytic activity 15, 16, 17 and OTUD4, which serves as a scaffold for USP enzymes 18."
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"We have shown here that a subset of E2 enzymes markedly stimulate OTUB1 cleavage of Lys48 linked polyubiquitin (XREF_FIG) and that the same set of OTUB1-E2 interactions are required for both OTUB1 non catalytic inhibition of E2 enzymes and E2 stimulation of OTUB1 XREF_BIBR, XREF_BIBR."
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"To investigate whether the inhibition of E2 by OTUB1 was the rate limiting step in its inhibition of SMAD3 polyubiquitylation in vitro, we set up an in vitro ubiquitylation assay with ubiquitin, E1, varying concentrations of E2, E3 and recombinant human SMAD3 in the presence or absence of 0.5 muM GST-OTUB1 (XREF_FIG)."
OTUB1 activates Genome polyprotein.
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OTUB1 activates Genome polyprotein. 3 / 3
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"Recently, several studies have described a non canonical mode of OTUB1 action in which OTUB1 inhibits the ubiquitylation of target proteins by binding to and inhibiting the E2 ubiquitin conjugating enzyme UBE2N (also known as UBC13) independent of its catalytic activity XREF_BIBR XREF_BIBR XREF_BIBR XREF_BIBR."
Genome polyprotein affects OTUB1
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Genome polyprotein binds OTUB1.
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OTUB1 binds Genome polyprotein. 10 / 61
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sparser
"During non‐canonical deubiquitination, OTUB1 preferentially binds to ubiquitin‐conjugated E2, which restricts ubiquitin transfer. [ xref ] Moreover, the binding surface of OTUB1/E2 interferes with the interaction between E2 and E3, which further inhibits ubiquitination. [ xref ] "
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"Together, the inhibitory profile of the OTUB1 mutants was fully consistent with the crystal structure of the Ub ~ E2 and OTUB1-Ub complex and demonstrated (1) that the E2 interaction surface on OTUB1, remote from its catalytic site, was dispensable for its DUB function, and (2) that both Ub interaction surfaces on OTUB1 were required for its isopeptidase activity, as they likely engage K48 linked di-Ub substrates."
Genome polyprotein activates OTUB1.
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Genome polyprotein activates OTUB1. 10 / 21
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"Since only uncharged E2 stimulates OTUB1 DUB activity while charged E2 ~ Ub represses OTUB1 under normal cellular concentrations of free ubiquitin, the relative proportion of charged versus uncharged E2s must be critical determinants of whether OTUB1-E2 complexes function as active DUBs in the cell."
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"We have shown here that a subset of E2 enzymes markedly stimulate OTUB1 cleavage of Lys48 linked polyubiquitin (XREF_FIG) and that the same set of OTUB1-E2 interactions are required for both OTUB1 non catalytic inhibition of E2 enzymes and E2 stimulation of OTUB1 XREF_BIBR, XREF_BIBR."
Genome polyprotein inhibits OTUB1.
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Genome polyprotein inhibits OTUB1. 5 / 5
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"Since only uncharged E2 stimulates OTUB1 DUB activity while charged E2 ~ Ub represses OTUB1 under normal cellular concentrations of free ubiquitin, the relative proportion of charged versus uncharged E2s must be critical determinants of whether OTUB1-E2 complexes function as active DUBs in the cell."
sparser
"For example, USP7 regulates the stability of both p53 and Mdm2 and maintains p53 ubiquitination levels; xref USP2 mediates the stability of Mdm2; xref USP10 modulates p53 localization and stability; xref OTUB1 abrogates p53 ubiquitination and activates p53. xref Interestingly, USP10 can stabilize both mutated and wild-type p53, with a dual role in tumorigenesis."
OTUB1 affects cell population proliferation
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OTUB1 activates cell population proliferation.
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OTUB1 activates cell population proliferation. 10 / 65
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"A growing body of literature demonstrates that the DUB Otubain 1 (OTUB1) regulates many cancer associated signaling pathways including MAPK, ERa, epithelial-mesenchymal transition (EMT), RHOa, mTORC1, FOXM1 and P53 to promote tumor cell survival, proliferation, invasiveness and therapeutic resistance."
OTUB1 inhibits cell population proliferation.
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OTUB1 affects Neoplasm Invasiveness
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OTUB1 activates Neoplasm Invasiveness.
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OTUB1 inhibits Neoplasm Invasiveness.
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"18 In here, we not only show that the potent oncogene FOXM1 is a target of OTUB1 but also present evidence to demonstrate that the oncogenic and genotoxic functions of OTUB1 depend on the expression of a functional FOXM1, suggesting that OTUB1 promotes cell proliferation and epirubicin resistance predominantly through targeting FOXM1."
"Focusing on <span class="match term1">Tau</span> deubiquitination, we here identify <span class="match term0">Otub1</span> as a <span class="match term1">Tau</span>-deubiquitinating enzyme. <span class="match term0">Otub1</span> directly affected Lys48-linked <span class="match term1">Tau</span> deubiquitination"
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"For instance, OTUB1 inhibits several E2 ubiquitin-conjugating enzymes through protein-protein interactions [42,43,44], and OTULIN interferes with endosomal trafficking by interacting with SNX27, a protein involved in protein trafficking and endocytosis of plasma membrane receptors [45]."
sparser
"For instance, OTUB1 inhibits several E2 ubiquitin-conjugating enzymes through protein-protein interactions [ xref , xref , xref ], and OTULIN interferes with endosomal trafficking by interacting with SNX27, a protein involved in protein trafficking and endocytosis of plasma membrane receptors [ xref ]."
sparser
"Indeed, YAP1 protein levels exhibit an increase in precancerous and invasive HNSCC, xref and the striking observation of endogenous YAP1 hyperactivation in tongue tissues leading to swift cancer development strongly implies the role of YAP1 in triggering the onset and progression of HNSCC. xref These findings suggest that OTUB1‐YAP1 axis may play an important role in HNSCC progression."
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"These findings suggest that OTUB1 might modulate YAP1 protein levels through its involvement in the ubiquitin‐proteasome pathway, thus regulating YAP1 stability.To advance our understanding of the role of YAP1 in the phenotypes driven by OTUB1 in HNSCC cells, we assessed the efficacy of YAP1 siRNA in mitigating the cell proliferation and invasion prompted."
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"These findings suggest that OTUB1 might modulate YAP1 protein levels through its involvement in the ubiquitin‐proteasome pathway, thus regulating YAP1 stability.To advance our understanding of the role of YAP1 in the phenotypes driven by OTUB1 in HNSCC cells, we assessed the efficacy of YAP1 siRNA in mitigating the cell proliferation and invasion prompted."
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"Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) mediates YAP phosphorylation and affects cellular energy pressure metabolism [32], while mammalian target of rapamycin complex-2 (mTORC2) directly phosphorylates YAP (Ser 463), enhancing YAP activity and promoting the malignant phenotype of glioblastoma [33]; the deubiquitinase OTUB1 reduces YAP ubiquitination levels and inhibits YAP degradation, thereby promoting the proliferation activity of gastric cancer cells [34]."
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"Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) mediates YAP phosphorylation and affects cellular energy pressure metabolism [32], while mammalian target of rapamycin complex-2 (mTORC2) directly phosphorylates YAP (Ser 463), enhancing YAP activity and promoting the malignant phenotype of glioblastoma [33]; the deubiquitinase OTUB1 reduces YAP ubiquitination levels and inhibits YAP degradation, thereby promoting the proliferation activity of gastric cancer cells [34]."
sparser
"To further explore the specific relationship between OTUB1 and β-catenin, the network association involved in OTUB1 and β-catenin was predicted via GENEMANIA online database, and the results showed that molecular and functional interaction between OTUB1 and β-catenin was undoubtedly ( xref B)."
sparser
"Although the relationship between OTUB1 and β-catenin has been introduced in colorectal cancer xref , our study further explained the more detailed interaction between OTUB1 and β-catenin, emphasizing the effects of the OTUB1/β-catenin axis in BLCA and the specific domain of interaction."
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"Subsequent experiments further suggested that OTUB1 promoted CRC malignancy by enhancing protein stability of beta-catenin, via inhibition of its protein degradation by UPP pathway, which indicated its crucial role in enhancement of CRC tumor cellular proliferative and chemo-resistant capabilities."
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"At the same time, a high level of N-cadherin expression blocks beta-catenin entry into the nucleus [XREF_BIBR], so the changes in beta-catenin mediated by OTUB1 were observed in the cytoplasm in our model, which might be the reason why TCF1, LEF1 were not activated in our models (Additional file 11 : Figure S9)."
OTUB1 affects apoptotic process
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OTUB1 activates apoptotic process.
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OTUB1 inhibits apoptotic process.
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OTUB1 inhibits apoptotic process. 10 / 19
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"Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells (OTUB1 LPC-KO) and human OTUB1 deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal and TNF challenge."
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"Recently, UBE2E1 was shown to autoubiquitinate itself in vitro in the presence or absence of the E3 ligase, RNF4 (30, 31), raising the possibility that OTUB1 may stabilize UBE2E1 by preventing autoubiquitination.To test the hypothesis that OTUB1 may directly inhibit UBE2E1, we assayed the autoubiquitinating activity of UBE2E1 in the presence and absence of OTUB1 in vitro."
"<span class="match term0">OTUB1</span> non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme <span class="match term1">UBE2E1</span> by preventing its autoubiquitination"
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"Although it is not known whether RNF4 stimulates UBE2E1 in vivo, our in vitro results raised the interesting possibility that OTUB1 could inhibit UBE2E1 autoubiquitination in cells, thereby accounting for the ability of OTUB1 to prevent UBE2E1 from being targeted to the proteasome."
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"Recently, UBE2E1 was shown to autoubiquitinate itself in vitro in the presence or absence of the E3 ligase, RNF4 (30, 31), raising the possibility that OTUB1 may stabilize UBE2E1 by preventing autoubiquitination.To test the hypothesis that OTUB1 may directly inhibit UBE2E1, we assayed the autoubiquitinating activity of UBE2E1 in the presence and absence of OTUB1 in vitro."
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"Resolution was extended by refinement at 3.3 A resolution against the P2 1 X-ray data set to an R factor / R free of 22.1/28.8%, with a doubling of the contents of the asymmetric unit The fold architectures of UbcH5b, OTUB1 and Ub have been described previously and do not deviate significantly in the Ub ~ UbcH5b and OTUB1-Ub complex (see XREF_SUPPLEMENTARY for sequence alignments and secondary structure assignments)."
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"Resolution was extended by refinement at 3.3 A resolution against the P2 1 X-ray data set to an R factor / R free of 22.1/28.8%, with a doubling of the contents of the asymmetric unit The fold architectures of UbcH5b, OTUB1 and Ub have been described previously and do not deviate significantly in the Ub ~ UbcH5b and OTUB1-Ub complex (see XREF_SUPPLEMENTARY for sequence alignments and secondary structure assignments)."
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"However, assays of OTUB1 stimulation by UBCH5B or UBCH5B ~ Ub over a range of ubiquitin concentrations (XREF_FIG) (XREF_SUPPLEMENTARY) showed that stimulation by UBCH5B is relatively insensitive to free ubiquitin, but that stimulation by UBCH5B ~ Ub decreases as a function of increasing concentration of free ubiquitin, dropping to low levels below ~ 1 microM free ubiquitin."
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"The importance of the OTUB1 N-terminal helix to its ability to be stimulated by UBCH5B, together with the role of these N-terminal residues in forming the proximal ubiquitin binding site of OTUB1 XREF_BIBR, XREF_BIBR, XREF_BIBR, suggested that UBCH5B may increase OTUB1 affinity for Lys48 diubiquitin via the proximal ubiquitin binding site."
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"Co‐IP experiment showed that, although the truncated OTUB1 lacking the UBA domain interacted with CCN6, the truncated OTUB1 lacking both UBA and linker domains failed to bind CCN6, indicating that the linker domain is needed for the binding between OTUB1 and CCN6 (Figure 3E).3.4
OTUB1 stabilizes CCN6 through the non-canonical function."
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"Although the precise mechanism by which OTUB1 induces RACK1 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and RACK1 as well as OTUB1’s ability to inhibit E2-conjugating enzymes recruited by the unknown E3 ligase contribute to RACK1 stabilization induced by OTUB1."
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"Although the precise mechanism by which OTUB1 induces RACK1 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and RACK1 as well as OTUB1’s ability to inhibit E2-conjugating enzymes recruited by the unknown E3 ligase contribute to RACK1 stabilization induced by OTUB1."
sparser
"Recent research has also found that OTUB1 maintains low levels of PD‐L1 ubiquitination, indicating its potential as a target in immune evasion related to PD‐L1/PD‐1 therapy and in the immunosuppression of cancer cells. [ xref , xref ] However, the interaction between OTUB1 and RAB8A in prostate cancer cells, and the role of circRNAs in this context, has not been reported."
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"We found that circ_0 005185 acts as a scaffold, facilitating the binding between the deubiquitinating enzyme OTUB1 and RAB8A and mediating their deubiquitination process, thereby stabilizing the protein levels of RAB8A and promoting primary cilium formation.Primary cilia are microtubule‐based organelles extending from the cell membrane that function as antennae to sense extracellular signals."
sparser
"Based on these observations, we hypothesized that circ_0 005185 mediates the deubiquitination of RAB8A by facilitating the binding of OTUB1 to RAB8A. This mechanism subsequently regulates the formation of primary cilia and the activation of the Hh signaling pathway, ultimately influencing the progression and drug resistance of prostate cancer."
sparser
"Hsa_circ_0005185 interacts with OTUB1 and RAB8A, facilitating the binding of the deubiquitinating enzyme OTUB1 to RAB8A. This interaction promotes RAB8A deubiquitination, thereby stabilizing RAB8A. The stabilized RAB8A enhances primary cilia regeneration and increases the production of GLI3R, a known suppressor of Hedgehog signaling."
sparser
"Hsa_circ_0005185 mediates the binding of the deubiquitinase OTUB1 to RAB8A, resulting in the deubiquitination of RAB8A. Consequently, the stable expression of RAB8A promotes the regeneration of primary cilia and enhances the production of GLI3R, an inhibitory factor in the Hedgehog signaling pathway, thereby suppressing AR activity and slowing the progression of CRPC."
OTUB1 affects Neoplasm Metastasis
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"Recent research has also found that OTUB1 maintains low levels of PD‐L1 ubiquitination, indicating its potential as a target in immune evasion related to PD‐L1/PD‐1 therapy and in the immunosuppression of cancer cells. [ xref , xref ] However, the interaction between OTUB1 and RAB8A in prostate cancer cells, and the role of circRNAs in this context, has not been reported."
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"We found that circ_0 005185 acts as a scaffold, facilitating the binding between the deubiquitinating enzyme OTUB1 and RAB8A and mediating their deubiquitination process, thereby stabilizing the protein levels of RAB8A and promoting primary cilium formation.Primary cilia are microtubule‐based organelles extending from the cell membrane that function as antennae to sense extracellular signals."
sparser
"Based on these observations, we hypothesized that circ_0 005185 mediates the deubiquitination of RAB8A by facilitating the binding of OTUB1 to RAB8A. This mechanism subsequently regulates the formation of primary cilia and the activation of the Hh signaling pathway, ultimately influencing the progression and drug resistance of prostate cancer."
sparser
"Hsa_circ_0005185 interacts with OTUB1 and RAB8A, facilitating the binding of the deubiquitinating enzyme OTUB1 to RAB8A. This interaction promotes RAB8A deubiquitination, thereby stabilizing RAB8A. The stabilized RAB8A enhances primary cilia regeneration and increases the production of GLI3R, a known suppressor of Hedgehog signaling."
sparser
"Hsa_circ_0005185 mediates the binding of the deubiquitinase OTUB1 to RAB8A, resulting in the deubiquitination of RAB8A. Consequently, the stable expression of RAB8A promotes the regeneration of primary cilia and enhances the production of GLI3R, an inhibitory factor in the Hedgehog signaling pathway, thereby suppressing AR activity and slowing the progression of CRPC."
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"Specifically, the deubiquitinating enzymes OTUB1 [138], OTU deubiquitinase 5 (OTUD5) [32,139], and ubiquitin specific peptidase 31 (USP31) [140] remove ubiquitination, inducing subsequent proteasomal degradation of GPX4, thus inhibiting ferroptosis-mediated tissue injury or tumor progression."
sparser
"In order to explore this concept, we performed a c-Maf-recognition element-driven luciferase-based screen against FDA-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
sparser
"It is essential for Otub1 to engage with c-Maf before preventing c-Maf polyubiquitination and degradation via the ubiquitin-proteasomal pathway, however, AVT can disrupt this interaction between Otub1 and c-Maf, which further abolishes the deubiquitinating activity of Otub1 towards c-Maf."
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"In order to explore this concept, we performed a c-Maf-recognition element driven luciferase based screen against FDA approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
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"Furthermore, the instability of PD-L1 produced by OTUB1 depletion stimulates the infiltration of more CD8 T cells and the production of more IFN-γ, both of which aid in the development of antitumor immunity against tumors.90 Another research describes a regulatory mechanism for OTUB1 that occurs upstream of the transcription factor."
"Mechanistically, we demonstrate that <span class="match term0">OTUB1</span> interacts with and removes K48-linked ubiquitin chains from the <span class="match term1">PD-L1</span> intracellular domain in a manner dependent on its deubiquitinase activity to hinder the degradation of <span class="match term1">PD-L1</span> through the ERAD pathway"
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"To further explore the role of U0126 in regulating YB-1 protein stability, we performed coimmunoprecipitation (co-IP) and found that the treatment with U0126 restored the interaction between YB-1 and OTUB1 (Fig. 4G), thereby reducing YB-1 ubiquitination modification (Fig. 4H) and proteasome degradation."
sparser
"To further explore the role of U0126 in regulating YB-1 protein stability, we performed coimmunoprecipitation (co-IP) and found that the treatment with U0126 restored the interaction between YB-1 and OTUB1 ( xref G ), thereby reducing YB-1 ubiquitination modification ( xref H ) and proteasome degradation."
sparser
"Study in vitro and in vivo indicated that hyperglycaemia caused the phosphorylation of S102 site of YB-1 in cardiomyocytes, which weakened the interaction between YB-1 and OTUB1, thus promoting the degradation of YB-1 through ubiquitin-proteasome pathway, leading to aggravation of diabetes cardiomyopathy (Ref. xref )."
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"This may help to understand whether phospho-FAT10, while inducing the deubiquitylation of TRAF3, could simultaneously enhance OTUB1 activity in removing K48-ubiquitin chains from RIG-I, thereby impairing its proteasomal degradation.It is interesting to note that the measured IFNβ levels differed always markedly between A549 OTUB1 knockout cells which were treated either with Poly (I:C), or which were infected with IAV (Fig 7E and F)."
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"Importantly, all of these values are up to almost an order of magnitude lower than the K d of each E2 for OTUB1 in the absence of diubiquitin, highlighting the potential for K48 polyubiquitin chains to drive association of OTUB1 with its E2 partners at E2 concentrations on the order of 1 muM or less (XREF_FIG)."
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"In summary, from these experiments, we conclude that the FAT10-mediated degradation of TRIM21 results into FAT10-mediated down-regulation of antiviral type-I IFN secretion, though other pathways modulated by FAT10 (OTUB1/TRAF3 axis) also contribute to this down-regulation.Our earlier study had shown that FAT10 KO mice infected with LCMV secreted higher levels of type-I IFNs (Mah et al, 2019)."
OTUB1 affects ferroptosis
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OTUB1 inhibits ferroptosis.
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OTUB1 inhibits ferroptosis. 10 / 18
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"96 Other SLC7A11/system Xc regulators include CD44 and OTUB1, which suppress ferroptosis by directly binding the SLC7A11 protein and increasing the stability of the latter.97 98 Beclin-1 (BECN1), a key autophagy regulator, on the other hand, inhibits system Xc by binding SLC7A11, and consequently promotes ferroptosis induced by system Xc inhibitors.99
GPX4 regulators."
OTUB1 activates ferroptosis.
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OTUB1 activates ferroptosis. 9 / 9
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"Additionally, our data suggest that skeletal muscle development induced by OTUB1 through the ferroptosis pathway may do duty for a potential target for treating skeletal muscle-related diseases.Interestingly, numerous studies have demonstrated a significant correlation between ferroptosis and autophagy ."
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"To further explore the role of U0126 in regulating YB-1 protein stability, we performed coimmunoprecipitation (co-IP) and found that the treatment with U0126 restored the interaction between YB-1 and OTUB1 (Fig. 4G), thereby reducing YB-1 ubiquitination modification (Fig. 4H) and proteasome degradation."
sparser
"To further explore the role of U0126 in regulating YB-1 protein stability, we performed coimmunoprecipitation (co-IP) and found that the treatment with U0126 restored the interaction between YB-1 and OTUB1 ( xref G ), thereby reducing YB-1 ubiquitination modification ( xref H ) and proteasome degradation."
sparser
"Study in vitro and in vivo indicated that hyperglycaemia caused the phosphorylation of S102 site of YB-1 in cardiomyocytes, which weakened the interaction between YB-1 and OTUB1, thus promoting the degradation of YB-1 through ubiquitin-proteasome pathway, leading to aggravation of diabetes cardiomyopathy (Ref. xref )."
reach
"Besides, when we blocked PI3K/AKT and/or MEK/ERK signaling by its specific inhibitor MK2206 and PD98059, the promotive effect of OTUB1-induced malignant behavior of HCC cells was also significantly reversed (Fig. 6d–q), demonstrating that OTUB1 performed the tumor-enhanced effects by effectively activating the AKT and ERK signaling pathway."
reach
"Besides, when we blocked PI3K/AKT and/or MEK/ERK signaling by its specific inhibitor MK2206 and PD98059, the promotive effect of OTUB1-induced malignant behavior of HCC cells was also significantly reversed (Fig. 6d–q), demonstrating that OTUB1 performed the tumor-enhanced effects by effectively activating the AKT and ERK signaling pathway."
sparser
"IL-15-stimulated AKT activation is negatively regulated by Otub1, which physically interacts with AKT and prevents its K63 ubiquitination and membrane translocation. xref Interestingly, in IL-15-exposed cells, Otub1 is relocated to the membrane compartment, a mechanism that enables Otub1 to inhibit AKT ubiquitination and activation induced by both IL-15 and TCR signals (Fig. xref )."
sparser
"Indeed, YAP1 protein levels exhibit an increase in precancerous and invasive HNSCC, xref and the striking observation of endogenous YAP1 hyperactivation in tongue tissues leading to swift cancer development strongly implies the role of YAP1 in triggering the onset and progression of HNSCC. xref These findings suggest that OTUB1‐YAP1 axis may play an important role in HNSCC progression."
sparser
"When Flag-tagged WT OTUB1 (Flag-OTUB1) was cotransfected with empty vector, Myc-SET7 or its enzymatically deficient mutant (Myc-SET7-H297A) ( xref ) in OTUB1 −/− H1299 cells, monomethylation of OTUB1 in the cells transfected with WT SET7 was higher than in the cells transfected with empty vector control, while monomethylation of OTUB1 in the cells transfected with Myc-SET7-H297A was similar to the cells transfected with empty vector control, suggesting that OTUB1 might be methylated by endogenous SET7 in these cells or OUTB1 might be methylated at K122 by another unknown methyltransferase ( xref E )."
sparser
"To further explore the specific relationship between OTUB1 and β-catenin, the network association involved in OTUB1 and β-catenin was predicted via GENEMANIA online database, and the results showed that molecular and functional interaction between OTUB1 and β-catenin was undoubtedly ( xref B)."
sparser
"Although the relationship between OTUB1 and β-catenin has been introduced in colorectal cancer xref , our study further explained the more detailed interaction between OTUB1 and β-catenin, emphasizing the effects of the OTUB1/β-catenin axis in BLCA and the specific domain of interaction."
sparser
"When Flag-tagged WT OTUB1 (Flag-OTUB1) was cotransfected with empty vector, Myc-SET7 or its enzymatically deficient mutant (Myc-SET7-H297A) ( xref ) in OTUB1 −/− H1299 cells, monomethylation of OTUB1 in the cells transfected with WT SET7 was higher than in the cells transfected with empty vector control, while monomethylation of OTUB1 in the cells transfected with Myc-SET7-H297A was similar to the cells transfected with empty vector control, suggesting that OTUB1 might be methylated by endogenous SET7 in these cells or OUTB1 might be methylated at K122 by another unknown methyltransferase ( xref E )."
sparser
"Researchers found that OTUB1 directly binds to TRAF6 and removes K63-linked polyubiquitination modifications on TRAF6 through its deubiquitinating enzyme activity, an effect that inhibits TRAF6-mediated ubiquitination and activation of ASK1, which in turn down-regulates the expression of lipid metabolism-related genes (CD36, Fabp1, Scd1, PPARG and PPARα) and collagen-related genes (Col1a1, Col3a1, and α-SMA), which ultimately attenuated NASH ( xref )."
reach
"On the other hand, the lack of effect of high OTUB1 expression levels on patients ' survival could be further explained by the alternative interactions of OTUB1 beyond RAS that for instance were reported to lead to the stabilization of p53 (Sun etal, 2012) or CK2 mediated OTUB1 nuclear translocation to affect DNA repair (Herhaus etal, 2015)."
sparser
"In order to explore this concept, we performed a c-Maf-recognition element-driven luciferase-based screen against FDA-approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
sparser
"It is essential for Otub1 to engage with c-Maf before preventing c-Maf polyubiquitination and degradation via the ubiquitin-proteasomal pathway, however, AVT can disrupt this interaction between Otub1 and c-Maf, which further abolishes the deubiquitinating activity of Otub1 towards c-Maf."
reach
"In order to explore this concept, we performed a c-Maf-recognition element driven luciferase based screen against FDA approved drugs and natural products, from which the generic cardiac glycoside lanatoside C (LanC) is found to prevent c-Maf de-ubiquitination and induces its degradation by disrupting the interaction of Otub1 and c-Maf."
reach
"Specifically, OTUB1 prevents ER-associated degradation of PD-L1 to contribute to immune suppression [6], inhibits Ras mono-ubiquitination to trigger lung cancer development [7], promotes RohA activation to induce prostate cancer metastasis [8], stabilizes ATF6 to facilitate bladder cancer growth [9], deubiquitinates and stabilizes FOXM1 to promote renal cell carcinoma progression [10], interacts with and stabilizes SLC7A11 to regulate ferroptosis [11], and stabilizes c-Myc to facilitate Myc-dependent multiple myeloma proliferation [12]."
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"OTUB1 overexpression in the H1993 cell line harboring wt KRAS led to a higher and more sustained activation of ERK1/2 phosphorylation (Fig XREF_FIG A), whereas the introduction of OTUB1 into KRAS-mutant A549 cells only slightly increased the activity of the MAPK pathway (Fig XREF_FIG B)."
reach
"Consistently with our observation that OTUB1 overexpression induces the MAPK cascade activation in cells with wt RAS, we found that higher levels of OTUB1 significantly correlated with increased levels of ERK1/2 phosphorylation in lung adenocarcinomas harboring wt KRAS (Pearson 's coefficient : 0.352; P-value : 0.013) (Fig XREF_FIG D and E), while mutant KRAS tumors exhibited in general higher levels of ERK1/2 phosphorylation (Fig XREF_FIG D and E)."
reach
"Stimulation of OTUB1-competent BMDCs with both TgPFN and LPS resulted in increased p38, ERK1/2, and JNK phosphorylation compared to that in OTUB1-deficient BMDCs (Supplementary Fig. 2g, h), demonstrating that OTUB1 augments the activation of both NF-κB and MAPKs upon the engagement of TLR4 and TLR11/12."
reach
"On the other hand, OTUB1 did not further accelerate anchorage independent colony formation of HEK TE cells overexpressing both a constitutively active MEK1 D218, D222 allele (MEKDD) and myr-AKT, further confirming that OTUB1 overexpression promotes tumorigenic transformation by inducing the MAPK cascade activation."
reach
"Co‐IP experiment showed that, although the truncated OTUB1 lacking the UBA domain interacted with CCN6, the truncated OTUB1 lacking both UBA and linker domains failed to bind CCN6, indicating that the linker domain is needed for the binding between OTUB1 and CCN6 (Figure 3E).3.4
OTUB1 stabilizes CCN6 through the non-canonical function."
sparser
"Researchers found that OTUB1 directly binds to TRAF6 and removes K63-linked polyubiquitination modifications on TRAF6 through its deubiquitinating enzyme activity, an effect that inhibits TRAF6-mediated ubiquitination and activation of ASK1, which in turn down-regulates the expression of lipid metabolism-related genes (CD36, Fabp1, Scd1, PPARG and PPARα) and collagen-related genes (Col1a1, Col3a1, and α-SMA), which ultimately attenuated NASH ( xref )."
reach
"Indeed, the ability of OTUB1 to inhibit RNF168 dependent ubiquitylation is independent of its catalytic activity, and is instead mediated by its binding to and inhibition of the E2 UBC13, which cooperates with RNF168, suggesting that E2 regulation could also represent a means to regulate the DDR pathway."
sparser
"However, the current research has several limitations: (1) insufficient mechanistic validation (e.g., lack of loss-of-function experiments via OTUB1 knockout); (2) undefined site specificity (unidentified critical ubiquitination sites mediating OTUB1-TGFBI interaction); and (3) unverified direct binding between curcumol and OTUB1 or its enzymatic activity modulation, which requires further validation through binding assays (e.g., surface plasmon resonance [SPR]) or enzyme activity tests."
sparser
"Future studies should employ structural biology analyses of OTUB1-TGFBI protein interaction, biochemical validation of direct curcumol–OTUB1 binding, and dose-dependent evaluation of angiogenesis inhibition in both in vitro and in vivo models to refine the mechanistic understanding."
sparser
"However, the current research has several limitations: (1) insufficient mechanistic validation (e.g., lack of loss-of-function experiments via OTUB1 knockout); (2) undefined site specificity (unidentified critical ubiquitination sites mediating OTUB1-TGFBI interaction); and (3) unverified direct binding between curcumol and OTUB1 or its enzymatic activity modulation, which requires further validation through binding assays (e.g., surface plasmon resonance [SPR]) or enzyme activity tests."
sparser
"Future studies should employ structural biology analyses of OTUB1-TGFBI protein interaction, biochemical validation of direct curcumol–OTUB1 binding, and dose-dependent evaluation of angiogenesis inhibition in both in vitro and in vivo models to refine the mechanistic understanding."
"Functionally, <span class="match term0">OTUB1</span> facilitates metastasis of esophageal squamous cell carcinoma (ESCC) through promoting <span class="match term1">Snail</span> protein stability."
reach
"Deubiquitinases (DUBs) also play an important role in the regulation of Snail1 protein stability, including USP3, USP11, USP13, DUB3, USP18, USP26, USP27X, USP37, USP47, OTUB1, and PSMD14, that have been shown to facilitate deubiquitination and stabilization of nuclear Snail1 in promoting cell proliferation, migration, and invasion ."
reach
"Deletion of the UBA domain disrupted the interaction between FGFR2 and OTUB1 (Fig. 3f), indicating that the interaction between OTUB1 and FGFR2 was dependent on the UBA domain of OTUB1, which is absent in OTUB2.The downregulated protein level of FGFR2 in OTUB1-deficient cells prompted us to test whether OTUB1 is a potential DUB for FGFR2."
sparser
"It’s well known that OTUB1 contains two domains: the N-terminal ubiquitin-association (UBA) domain and the C-terminal ovarian tumor (OTU) domain. xref Deletion of the UBA domain disrupted the interaction between FGFR2 and OTUB1 (Fig. xref ), indicating that the interaction between OTUB1 and FGFR2 was dependent on the UBA domain of OTUB1, which is absent in OTUB2."
OTUB1 affects Endometriosis
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MiR-542-3p affects OTUB1
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MiR-542-3p decreases the amount of OTUB1.
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"For example, miR-542-3p expressions are greatly down-regulated in esophageal cancer, and miR-542-3p can inhibit the migration and aggressiveness of esophageal cancer cells by inhibiting OTUB1 expression [17]; in osteosarcoma, miR-542-3p can curb cell proliferative, migrative and aggressive abilities via targeting ILK [18]; in ovarian cancer, miR-542-3p can target CDK14 to inhibit tumorigenesis [19]; in bladder cancer, importantly, miR-542-3p expression is significantly impaired, and this miRNA can inhibit the viability of BC cells [20]."
MiR-542-3p inhibits OTUB1.
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MiR-542-3p increases the amount of OTUB1.
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MiR-542-3p binds OTUB1.
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"Although the precise mechanism by which OTUB1 induces RACK1 stabilization requires further elucidation, it is very likely that the binding between OTUB1 and RACK1 as well as OTUB1’s ability to inhibit E2-conjugating enzymes recruited by the unknown E3 ligase contribute to RACK1 stabilization induced by OTUB1."
eidos
"PKP3 upregulates OTUB1 expression by increasing OTUB1 mRNA stability To test whether PKP3-mediated OTUB1 upregulation is posttranscriptional or transcriptional , we constructed and transfected a luciferase reporter plasmid containing a promoter fragment of OTUB1 into NSCLC cells stably overexpressing PKP3 ."
reach
"Another study revealed that circIGF2BP3 functioned as the molecular sponge of miR-328-3p and miR-3173-5p to upregulate plakophilin 3 (PKP3) expression, thereby increasing ovarian tumor (OTU) family deubiquitinase ubiquitin aldehyde binding 1 (OTUB1) level and facilitating PD-L1 deubiquitination [8]."
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"31
Competitive binding of miR‐328‐3p and miR‐3173‐5p to circIGF2BP3 results in the upregulation of PKP3 expression, which promotes deubiquitinating enzyme otubain‐1 (OTUB1) expression by increasing its mRNA stability, and then prevents the proteasomal degradation of programmed cell death 1 ligand 1 (PD‐L1) by inducing its deubiquitination, and ultimately inhibits the activation and infiltration of CD8 T cells in the tumor region and thus facilitates tumor immune evasion in NSCLC."
OTUB1 affects immune response
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OTUB1 inhibits immune response.
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OTUB1 activates immune response.
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sparser
"The RIG-I tetramer translocates to mitochondrial membrane, where it activates downstream effectors including IRF3, IRF7, and NF-kB to produce type-I Interferon (IFN-I) ( xref ). xref found OTUB1 activates RIG-I at mitochondria and achieves this function through both DUB activity and E2-blocking activity."
sparser
"Both human and their homologs in grouper, Epinephelus coioides (OTUB1/2 and EcOTUB1/2), interact with TRAF3 and TRAF6, deubiquitinating them to attenuate virus-induced activation of IRF3 and NF-κB and suppress virus-triggered type I interferon (IFN) induction and promote viral replication. xref , xref Meanwhile, OTUB1 also activates RIG-I (retinoic acid-inducible gene I)-dependent antiviral responses through a dual mechanism: K48 polyubiquitin hydrolysis and complex formation with UbcH5c—a process antagonized by influenza A virus (IAV) NS1 protein-mediated OTUB1 degradation. xref This evolutionary arms race between host Otubains and viral evasion strategies underscores their fundamental role in antiviral defense, while highlighting the therapeutic potential of developing targeted Otubain modulators."
OTUB1 increases the amount of OTUB1.
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OTUB1 activates OTUB1.
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"These data suggest that SET7 and OTUB1 do not affect each other at protein level although they directly associate in cells.As reported previously, phosphorylation of OTUB1 at Serine 16 by Casein kinase 2 causes nuclear accumulation of OTUB1 (33), we sought to know whether SET7-mediated methylation of OTUB1 at K122 could alter subcellular localization of OTUB1."
OTUB1 inhibits OTUB1.
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OTUB1 affects glycolytic process
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"OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.|We show that OTUB1 negatively regulates transcription mediated by ERalpha in transient reporter gene assays and transcription mediated by endogenous ERalpha in Ishikawa endometrial cancer cells."
"OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.|We show that OTUB1 negatively regulates transcription mediated by ERalpha in transient reporter gene assays and transcription mediated by endogenous ERalpha in Ishikawa endometrial cancer cells."
sparser
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity-independent non-canonical mechanism."
reach
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity independent non canonical mechanism."
sparser
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity-independent non-canonical mechanism."
reach
"We found that OTUB1 directly interacted with DEPTOR via its N-terminal domain, deubiquitinated DEPTOR, and thereby stabilized DEPTOR in a Cys-91-independent but Asp-88-dependent manner, suggesting that OTUB1 targets DEPTOR for deubiquitination via a deubiquitinase activity independent non canonical mechanism."
sparser
"These E2 enzymes have EC 50 values in the single digit micromolar range and lower the K M of OTUB1 for its substrate to 6.6 – 14 μM. Since the concentration of UBE2D3 alone has been reported to be 1.7 μM in MEF cells xref and the effective concentration of UBE2D3 needed to stimulate the DUB activity of OTUB1 is 1.6 μM ( xref ), it is likely that OTUB1:UBE2D3 form a stimulated DUB complex in cells."
sparser
"For example, (a) Ubiquitin transfer blockade: In multiple myeloma, OTUB1 interacted with the E2 enzyme UBE2D3 to inhibit ubiquitination of the transcription factor c-Maf, stabilizing its expression and promoting tumor cell survival ( xref ). (b) Direct target protein binding: OTUB1 suppressed ubiquitination of proteins (e.g., HIF-1α and RACK1) through non-catalytic binding, thereby driving tumor progression ( xref , xref ). (c) Phosphorylation-dependent functional switching: Phosphorylation of the Tyr26 residue in OTUB1 enabled its interaction with the cell cycle regulator p27, modulating p27 stability and cell cycle progression ( xref )."
OTUB1 affects Prostatic Neoplasms
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OTUB1 activates Prostatic Neoplasms. 10 / 10
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eidos
"Although we have found that otub1 promoted the proliferation and progression of PCa via mediating and stabling Cyclin E1 , in which one ubiquitination enzyme directly causing to the ubiquitination degradation of Cyclin E1 remains unclear , and the manner of OTUB1 regulating the expression of Cyclin E1 directly or indirectly are still yet not determined ."
reach
"Here, inferred from the modulation of OTUB1 by FIH, an important regulator of HIF pathway, we further identified when FIH loses its suppressive role on the non-canonical inhibition ubiquitination activity of OTUB1 under hypoxia, OTUB1 enhances HIF-1α activity, uncovering a connection among FIH/OTUB1/HIF-1α."
reach
"Furthermore, ectopic expression of OTUB1 also increased protein levels of co-transfected HIF-1α-DM (in which two Proline residues [P402 and P564] are mutated to Alanine residues) and HIF-1α-TM (in which two Proline residues [P402 and P564] and one Asparagine residue [N803] is mutated to Alanine residue) (Fig. 5D, E), suggesting that the stabilization of HIF-1α protein by OTUB1 might be independent of hydroxylation mediated by PHDs and FIH."
OTUB1 affects Carcinogenesis
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sparser
"Studies have shown that the deubiquitinating enzyme OTUB1, which can bind the CD44 (cluster of differentiation-44), is recruited under the effect of removing the ubiquitin chain on SLC7A11 to prevent its degradation through the proteasome and improve its stability, thereby inhibiting the occurrence of ferroptosis in tumors ( xref )."
reach
"Although the direct interaction of CD44 and OTUB1 is much lower in comparison to OTUB1-xCT interaction, nevertheless, this three-protein complex is thought to stabilize xCT more effectively, possibly further enhancing chemoresistance.Another player involved in CD44v9-xCT complex stabilization is mucin 1 (MUC1) – a transmembrane glycoprotein commonly overexpressed in a plethora of cancers including lung, colon, breast, pancreatic and ovarian cancers (Chen et al., 2021; Figure 4A)."
reach
"Studies have shown that the deubiquitinating enzyme OTUB1, which can bind the CD44 (cluster of differentiation-44), is recruited under the effect of removing the ubiquitin chain on SLC7A11 to prevent its degradation through the proteasome and improve its stability, thereby inhibiting the occurrence of ferroptosis in tumors (Liu et al., 2019)."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
sparser
"Studies have shown that the deubiquitinating enzyme OTUB1, which can bind the CD44 (cluster of differentiation-44), is recruited under the effect of removing the ubiquitin chain on SLC7A11 to prevent its degradation through the proteasome and improve its stability, thereby inhibiting the occurrence of ferroptosis in tumors ( xref )."
reach
"Although the direct interaction of CD44 and OTUB1 is much lower in comparison to OTUB1-xCT interaction, nevertheless, this three-protein complex is thought to stabilize xCT more effectively, possibly further enhancing chemoresistance.Another player involved in CD44v9-xCT complex stabilization is mucin 1 (MUC1) – a transmembrane glycoprotein commonly overexpressed in a plethora of cancers including lung, colon, breast, pancreatic and ovarian cancers (Chen et al., 2021; Figure 4A)."
reach
"Studies have shown that the deubiquitinating enzyme OTUB1, which can bind the CD44 (cluster of differentiation-44), is recruited under the effect of removing the ubiquitin chain on SLC7A11 to prevent its degradation through the proteasome and improve its stability, thereby inhibiting the occurrence of ferroptosis in tumors (Liu et al., 2019)."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
sparser
"Negative staining EM shows that one molecule of OTU1 binds to one VCP hexamer, and isothermal titration calorimetry suggests that the two proteins bind with a KD of 0.71 μM. Analytical size exclusion chromatography and isothermal titration calorimetry demonstrates that OTU1 can bind VCP in both the presence and absence of a heterodimer formed by ubiquitin fusion degradation protein 1 and nuclear localization protein 4."
sparser
"A coimmunoprecipitation (co-IP) assay using mutant PD-L1 or OTUB2 proteins with different structural domains deleted revealed the involvement of the ICD (261–290) of PD-L1 in the interaction with OTUB2 and the OTU domain (44–234) of OTUB2 in the interaction with PD-L1 (Fig. xref )."
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
OTUB1 affects ubiquitination
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7
sparser
"Negative staining EM shows that one molecule of OTU1 binds to one VCP hexamer, and isothermal titration calorimetry suggests that the two proteins bind with a KD of 0.71 μM. Analytical size exclusion chromatography and isothermal titration calorimetry demonstrates that OTU1 can bind VCP in both the presence and absence of a heterodimer formed by ubiquitin fusion degradation protein 1 and nuclear localization protein 4."
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"We found that although levels of NS2 conjugated with V5-Ub were substantially reduced if HEK293T cells were cotransfected with pFlag-OTUB1 (Fig 5B, lanes 3, 4), no reduction of Ub-HA-NS2 was observed if cells were cotransfected with pFlag-mOTUB1 (Fig 5B, lane 5), indicating that OTUB1 deubiquitinates NS2 through its catalytic activity."
reach
"Our study sheds light on the critical viral-host interaction between NS2 and OTUB1 that facilitates viral propagation (Figs 8 and 10), and further research into the changes in quantity and locality of OTUB1 following IAV infection may be warranted, in order to better understand how IAV utilizes host factors to enhance viral proliferation."
sparser
"A coimmunoprecipitation (co-IP) assay using mutant PD-L1 or OTUB2 proteins with different structural domains deleted revealed the involvement of the ICD (261–290) of PD-L1 in the interaction with OTUB2 and the OTU domain (44–234) of OTUB2 in the interaction with PD-L1 (Fig. xref )."
sparser
"Next, Kaplan-Meier's survival analysis was performed to examine the expression of five deubiquitinating enzymes in 117 NSCLC patients (GEO Submission: GSE13213) and revealed that the higher expression of OTUB1 and OTUB2 was significantly associated with poor patient prognosis (Figure xref B-EandFigure xref E)."
sparser
"OTU1 and OTU2 ( R. radiotolerans ) associated to the meteorites ( p = 0.034), as did OTU5 ( Blastococcus sp.) p = 0.034, OTU6 ( G. pulveris ) p = 0.034, OTU12 (Chloroflexi) p = 0.028, OTU15 ( B. jejuensis ) p = 0.034, OTU19 (Frankiales) p = 0.034, OTU21 ( D. navajonensis ) p = 0.034, and OTU23 ( Rubrobacter sp.) p = 0.032."
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"We demonstrate that E2F1 activates the transcription of TMPO-AS1, which, in turn, facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinase; consequently, the E2F1 protein levels are increased via stabilization, promoting BC malignant phenotypes."
reach
"NS1 sequesters the RIG-I co-factors 14-3-3ε, OTUB1, and signaling molecule TRAF3 and interferes with the translocation of RIG-I to mitochondrial membrane [164,259] and the formation of MAVS–TRAF3 complex [260,261] (Figure 5), respectively.PB1-F2 is another non-structural protein that IAV employs to antagonize the RIG-I signaling."
reach
"Previous research has shown that during viral infection, OTUB1 translocates from the nucleus to the mitochondrial membrane, where it activates RIG-I-dependent immune signaling; however, IAV NS1 can trigger proteasomal degradation of cellular OTUB1 to dampen this antiviral immune response [32]."
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"We demonstrate that E2F1 activates the transcription of TMPO-AS1, which, in turn, facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), a deubiquitinase; consequently, the E2F1 protein levels are increased via stabilization, promoting BC malignant phenotypes."
OTUB1 affects ubiquitylation
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sparser
"Recently, several studies have described a non-canonical mode of OTUB1 action in which OTUB1 inhibits the ubiquitylation of target proteins by binding to and inhibiting the E2 ubiquitin-conjugating enzyme UBE2N (also known as UBC13) independent of its catalytic activity xref xref xref xref ."
OTUB1 affects signal transduction
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OTUB1 activates signal transduction.
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OTUB1 activates signal transduction. 5 / 5
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"Besides, when we blocked PI3K/AKT and/or MEK/ERK signaling by its specific inhibitor MK2206 and PD98059, the promotive effect of OTUB1-induced malignant behavior of HCC cells was also significantly reversed (Fig. 6d–q), demonstrating that OTUB1 performed the tumor-enhanced effects by effectively activating the AKT and ERK signaling pathway."
OTUB1 inhibits signal transduction.
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OTUB1 affects proteolysis
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OTUB1 inhibits proteolysis.
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OTUB1 inhibits proteolysis. 4 / 4
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"Meanwhile, the expression of NDUFS2 was overexpressed significantly after being transfected with OE-NDUFS2 plasmid, but the overexpression was abolished by co-transfection with sh-OTUB1 plasmids (Fig. 6D), suggesting that OTUB1 could promotes the expression of NDUFS2.To further test that whether OTUB1 could promote NDUFS2 protein degradation, MG132, chloroquine and CHX assay were used."
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"We had previously demonstrated that human Otub1 protein leads to degradation of human GRAIL protein, and in a similar manner, murine Otub1 protein leads to murine GRAIL protein degradation (supplemental Fig. 3).4 Ex vivo isolated naive CD4 T cells express no Otub1 protein, thus allowing GRAIL expression (XREF_FIG, first lane), despite the presence of detectable Otub1 mRNA as mTOR mediated protein translation is inactive in these cells."
OTUB1 activates proteolysis.
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OTUB1 affects polyubiquitin chains
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OTUB1 affects NS2
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sparser
"The paradox in which OTUB1 appears to promote both an innate anti-IAV immune response as well as IAV proliferation can be explained by the results of our study, which shows that OTUB1 interacts with NS2 to set the stage for viral cRNA synthesis and is critical for vRNP nuclear export (Figs xref and xref )."
sparser
"Our study sheds light on the critical viral-host interaction between NS2 and OTUB1 that facilitates viral propagation (Figs xref and xref ), and further research into the changes in quantity and locality of OTUB1 following IAV infection may be warranted, in order to better understand how IAV utilizes host factors to enhance viral proliferation."
OTUB1 affects Deubiquitinase
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6
OTUB1 inhibits Deubiquitinase.
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2
OTUB1 activates Deubiquitinase.
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4
OTUB1 affects 4'-epidoxorubicin
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8
OTUB1 activates 4'-epidoxorubicin.
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6
OTUB1 activates 4'-epidoxorubicin. 6 / 6
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6
reach
"18 In here, we not only show that the potent oncogene FOXM1 is a target of OTUB1 but also present evidence to demonstrate that the oncogenic and genotoxic functions of OTUB1 depend on the expression of a functional FOXM1, suggesting that OTUB1 promotes cell proliferation and epirubicin resistance predominantly through targeting FOXM1."
OTUB1 inhibits 4'-epidoxorubicin.
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2
OTUB1 inhibits 4'-epidoxorubicin. 2 / 2
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2
NS2 affects OTUB1
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8
sparser
"The paradox in which OTUB1 appears to promote both an innate anti-IAV immune response as well as IAV proliferation can be explained by the results of our study, which shows that OTUB1 interacts with NS2 to set the stage for viral cRNA synthesis and is critical for vRNP nuclear export (Figs xref and xref )."
sparser
"Our study sheds light on the critical viral-host interaction between NS2 and OTUB1 that facilitates viral propagation (Figs xref and xref ), and further research into the changes in quantity and locality of OTUB1 following IAV infection may be warranted, in order to better understand how IAV utilizes host factors to enhance viral proliferation."
FIH affects OTUB1
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8
FIH hydroxylates OTUB1.
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5
FIH binds OTUB1.
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3
reach
"Collectively, these data suggest that OTUB1 facilitates hypoxia adaptation, which might benefit cancer progression.In order to determine whether the formation of FIH and OTUB1 heterodimers could affect OTUB1’s regulation on hypoxia signaling, we used FG4592 to stabilize HIF-1α under normoxia."
sparser
"Crucially, we identified a specific interaction between Talin2 and OTUB1, enabling a novel precision therapeutic strategy: targeted small‐molecule inhibitors designed to disrupt Talin2/OTUB1 binding affinity. [ xref ] This approach achieves dual therapeutic effects by accelerating Talin2 degradation, blocking mechano‐inflammatory signal conversion, and promoting ECM synthesis."
OTUB1 affects cell migration
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7
sparser
"Crucially, we identified a specific interaction between Talin2 and OTUB1, enabling a novel precision therapeutic strategy: targeted small‐molecule inhibitors designed to disrupt Talin2/OTUB1 binding affinity. [ xref ] This approach achieves dual therapeutic effects by accelerating Talin2 degradation, blocking mechano‐inflammatory signal conversion, and promoting ECM synthesis."
OTUB1 affects Cell Survival
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2
5
OTUB1 activates Cell Survival. 7 / 7
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2
5
reach
"A growing body of literature demonstrates that the DUB Otubain 1 (OTUB1) regulates many cancer associated signaling pathways including MAPK, ERa, epithelial-mesenchymal transition (EMT), RHOa, mTORC1, FOXM1 and P53 to promote tumor cell survival, proliferation, invasiveness and therapeutic resistance."
reach
"This intricate relationship is further exemplified in NSCLC, in which the circular RNA insulin-like growth factor 2 mRNA-binding protein 3 (circIGF2BP3) modulates OTUB1 levels, counteracts the ubiquitinated degradation of PD-L1, and suppresses CD8 T-cell function, ultimately facilitating immune evasion [77]."
1
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1
3
OTUB1 affects necroptotic process
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2
4
OTUB1 inhibits necroptotic process. 6 / 6
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2
4
reach
"Combined in vivo and in vitro experiments comprising mice lacking OTUB1 specifically in liver parenchymal cells (OTUB1 LPC-KO) and human OTUB1 deficient HepG2 cells revealed that OTUB1 prevented hepatocyte necroptosis but not apoptosis upon infection with Lm and DGal and TNF challenge."
OTUB1 affects endoplasmic reticulum
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6
OTUB1 inhibits endoplasmic reticulum.
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2
OTUB1 inhibits endoplasmic reticulum. 2 / 2
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2
OTUB1 binds endoplasmic reticulum.
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2
OTUB1 activates endoplasmic reticulum.
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2
reach
"Subsequent experiments further suggested that OTUB1 promoted CRC malignancy by enhancing protein stability of beta-catenin, via inhibition of its protein degradation by UPP pathway, which indicated its crucial role in enhancement of CRC tumor cellular proliferative and chemo-resistant capabilities."
eidos
"All cell lysates were subjected to WB assays as indicated AVT interferes with the interaction between Otub1 and c-Maf to increase c-Maf polyubiquitination AVT was identified from the Otub1 / c-Maf system , while Otub1 interacts with c-Maf and prevents its polyubiquitination as its deubiquitinase , therefore , we wondered whether AVT can inhibit Otub1 activity toward c-Maf ubiquitination ."
reach
"Another study revealed that circIGF2BP3 functioned as the molecular sponge of miR-328-3p and miR-3173-5p to upregulate plakophilin 3 (PKP3) expression, thereby increasing ovarian tumor (OTU) family deubiquitinase ubiquitin aldehyde binding 1 (OTUB1) level and facilitating PD-L1 deubiquitination [8]."
OTUB1 affects localization
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5
OTUB1 activates localization. 5 / 5
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5
reach
"OTUB1 has been reported to enhance membrane localization and promote the activation of wild-type KRAS—but not KRAS mutants—by suppressing the enzymatic activity of E2 enzymes ubiquitin-conjugating enzyme 13 (UBC13) and ubiquitin-conjugating enzyme E2 D3 (UBE2D3), indicating that OTUB1 regulates wild-type KRAS in an indirect manner ."
OTUB1 affects cell death
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1
3
OTUB1 inhibits cell death.
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1
1
OTUB1 activates cell death.
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2
reach
"Another study revealed that circIGF2BP3 functioned as the molecular sponge of miR-328-3p and miR-3173-5p to upregulate plakophilin 3 (PKP3) expression, thereby increasing ovarian tumor (OTU) family deubiquitinase ubiquitin aldehyde binding 1 (OTUB1) level and facilitating PD-L1 deubiquitination [8]."
reach
"These data suggest that OTU1 negatively regulates expression of DA1 and DA2 and that its loss of function results in transcriptional activation of these target genes.DA1, a ubiquitin-binding protein, and DA2, a RING-type E3 ubiquitin ligase, are known to interact with each other and negatively regulate the seed and organ size in Arabidopsis (Du et al., 2014, Li and Li, 2014, Li and Li, 2016, Xia et al., 2013)."
OTUB1 affects MSH2 ubiquitination
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5
sparser
"In the in vitro ubiquitination assay, individual Flag-tagged substrates (MSH2, FOXM1, and DEPTOR) were incubated with GST-OTUB1 (WT, C91A, or D88A) and HA-Ub in a ubiquitination system containing rabbit reticulocyte lysate (RRL), as described previously ( xref ), and ubiquitinated substrates were visualized by western blotting using a Ub antibody."
reach
"Besides, when we blocked PI3K/AKT and/or MEK/ERK signaling by its specific inhibitor MK2206 and PD98059, the promotive effect of OTUB1-induced malignant behavior of HCC cells was also significantly reversed (Fig. 6d–q), demonstrating that OTUB1 performed the tumor-enhanced effects by effectively activating the AKT and ERK signaling pathway."
OTUB1 affects DNA Damage
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4
reach
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment (Figure 3h–3i)."
sparser
"Having identified NJH-2-057 as a DUBTAC that was capable of stabilizing mutant CFTR in cells, we next sought to confirm the formation of a ternary complex between CFTR, NJH-2-057, and OTUB1 in vitro using recombinant protein and native mass spectrometry (MS)-based approaches ( xref – xref )."
sparser
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment ( xref – xref )."
sparser
"In the in vitro ubiquitination assay, individual Flag-tagged substrates (MSH2, FOXM1, and DEPTOR) were incubated with GST-OTUB1 (WT, C91A, or D88A) and HA-Ub in a ubiquitination system containing rabbit reticulocyte lysate (RRL), as described previously ( xref ), and ubiquitinated substrates were visualized by western blotting using a Ub antibody."
reach
"Deletion of the UBA domain disrupted the interaction between FGFR2 and OTUB1 (Fig. 3f), indicating that the interaction between OTUB1 and FGFR2 was dependent on the UBA domain of OTUB1, which is absent in OTUB2.The downregulated protein level of FGFR2 in OTUB1-deficient cells prompted us to test whether OTUB1 is a potential DUB for FGFR2."
sparser
"It’s well known that OTUB1 contains two domains: the N-terminal ubiquitin-association (UBA) domain and the C-terminal ovarian tumor (OTU) domain. xref Deletion of the UBA domain disrupted the interaction between FGFR2 and OTUB1 (Fig. xref ), indicating that the interaction between OTUB1 and FGFR2 was dependent on the UBA domain of OTUB1, which is absent in OTUB2."
reach
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment (Figure 3h–3i)."
sparser
"Having identified NJH-2-057 as a DUBTAC that was capable of stabilizing mutant CFTR in cells, we next sought to confirm the formation of a ternary complex between CFTR, NJH-2-057, and OTUB1 in vitro using recombinant protein and native mass spectrometry (MS)-based approaches ( xref – xref )."
sparser
"While the highest intensity signals corresponded to unmodified OTUB1 and the ΔF508-harboring CFTR nucleotide-binding domain used in this experiment, potentially indicating low levels of target engagement under these experimental conditions, we observed significant CFTR-OTUB1 complex formation with NJH-2-057 treatment, but not with DMSO vehicle or EN523 treatment ( xref – xref )."
sparser
"IL-15-stimulated AKT activation is negatively regulated by Otub1, which physically interacts with AKT and prevents its K63 ubiquitination and membrane translocation. xref Interestingly, in IL-15-exposed cells, Otub1 is relocated to the membrane compartment, a mechanism that enables Otub1 to inhibit AKT ubiquitination and activation induced by both IL-15 and TCR signals (Fig. xref )."
Valproic acid affects OTUB1
4
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Tumor necrosis factor receptor affects OTUB1
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4
reach
"Through immunoprecipitation-mass spectrometry (IP-MS) analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63 (K63)-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway."
reach
"The deubiquitinating enzyme ubiquitin aldehyde binding 1 (OTUB1) directly binds to tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its lysine 63-linked polyubiquitination, thereby inhibiting the activation of ASK1 and its downstream MAPK pathway 73.The ubiquitin system also plays an important role in the activation of other pathways."
Bisphenol A affects OTUB1
4
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reach
"Our study sheds light on the critical viral-host interaction between NS2 and OTUB1 that facilitates viral propagation (Figs 8 and 10), and further research into the changes in quantity and locality of OTUB1 following IAV infection may be warranted, in order to better understand how IAV utilizes host factors to enhance viral proliferation."
OTUB1 affects tumor necrosis factor receptor
|
4
reach
"Through immunoprecipitation-mass spectrometry (IP-MS) analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63 (K63)-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway."
reach
"The deubiquitinating enzyme ubiquitin aldehyde binding 1 (OTUB1) directly binds to tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its lysine 63-linked polyubiquitination, thereby inhibiting the activation of ASK1 and its downstream MAPK pathway 73.The ubiquitin system also plays an important role in the activation of other pathways."
OTUB1 affects regulation of cell cycle
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4
OTUB1 inhibits regulation of cell cycle.
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2
OTUB1 inhibits regulation of cell cycle. 2 / 2
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2
OTUB1 activates regulation of cell cycle.
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2
OTUB1 affects ossification
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4
OTUB1 affects interleukin-6 production
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4
OTUB1 affects interleukin-12 production
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4
OTUB1 activates interleukin-12 production. 4 / 4
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4
reach
"Reduced phosphorylation of TAK1, IκBα, and p65 was detected in OTUB1-deficient BMDCs upon stimulation with TgPFN (Fig. 2g), suggesting that OTUB1 is required for the full-fledged activation of NF-κB. To reinforce the assertion that OTUB1 promotes IL-12 production by increasing NF-κB activity, we studied the effect of IKK inhibition on TgPFN-induced cytokine production in OTUB1-sufficient and OTUB1-deficient BMDCs."
OTUB1 affects inflammatory response
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4
OTUB1 affects development endometriosis
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4
reach
"The deubiquitinating enzyme ubiquitin aldehyde binding 1 (OTUB1) directly binds to tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its lysine 63-linked polyubiquitination, thereby inhibiting the activation of ASK1 and its downstream MAPK pathway 73.The ubiquitin system also plays an important role in the activation of other pathways."
OTUB1 affects Renin-Angiotensin System
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3
1
OTUB1 affects HSF1 protein stability
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4
OTUB1 affects DNA-templated transcription
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4
reach
"These data suggest that OTU1 negatively regulates expression of DA1 and DA2 and that its loss of function results in transcriptional activation of these target genes.DA1, a ubiquitin-binding protein, and DA2, a RING-type E3 ubiquitin ligase, are known to interact with each other and negatively regulate the seed and organ size in Arabidopsis (Du et al., 2014, Li and Li, 2014, Li and Li, 2016, Xia et al., 2013)."
Phospho-SMAD2/3 affects OTUB1
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3
Arf-1 affects OTUB1
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3
Ubv.B1.1 affects OTUB1
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3
sparser
"Of the 120 SRP-OTUs, the majority (> 75%) were found to be lake-specific, as they were observed in high relative abundance in only single lake, and only two SRP-OTUs (SRP-OTU1 affiliated with Halomonas ) and (SRP-OTU8 affiliated with Shewanlla ) were present in high relative abundance in all lakes."
TMPO-AS1 affects OTUB1
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3
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
reach
"Two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) showed that SLC7A11, OTUB1, and SLC3A2 were detected in association with the ~150-kDa complex (Fig. 2B), and co-immunoprecipitation analysis further confirmed the association between SLC7A11, SLC3A2, and OTUB1 after IL-1β stimulation (Fig. 2C)."
OTUB1 affects ubiquitination FOXM1
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3
OTUB1 affects phospho-SMAD2/3
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3
OTUB1 affects innate immune response
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3
OTUB1 affects gene expression
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3
OTUB1 affects cytokine production
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3
OTUB1 activates cytokine production. 3 / 3
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3
reach
"In addition, engagement of TLR2, TLR7, and TLR9, which all signal via MyD88, and TLR3, which signals in a MyD88-independent manner through TRIF, resulted in significantly reduced IL-12, TNF, and IL-6 production by OTUB1-deficient BMDCs (Supplementary Fig. 2c), illustrating the stimulatory role of OTUB1 in proinflammatory TLR signaling.To understand how OTUB1 promotes cytokine production in DCs, we stimulated FLT3L-expanded BMDCs with TLA (Fig. 2c), TgPFN (Fig. 2d), and LPS (Fig. 2e) and analyzed signaling molecules by WB analysis."
OTUB1 affects arf-1
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3
OTUB1 affects Ubv.B1.1
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3
sparser
"Of the 120 SRP-OTUs, the majority (> 75%) were found to be lake-specific, as they were observed in high relative abundance in only single lake, and only two SRP-OTUs (SRP-OTU1 affiliated with Halomonas ) and (SRP-OTU8 affiliated with Shewanlla ) were present in high relative abundance in all lakes."
OTUB1 affects UBE2E1 autoubiquitination
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3
OTUB1 affects TMPO-AS1
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3
reach
"The interactions between E2F1, OTUB1, and TMPO-AS1 were predicted via Agostini et al. introduced catRAPID (http://s.tartaglialab.com/page/catrapid_group), a server to identify the interaction of RNA and protein and Tuvshinjargal et al. developed a web server named PRIdictor (http://bclab.inha.ac.kr/pridictor) to reveal mutual binding in protein and RNA."
reach
"Two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) showed that SLC7A11, OTUB1, and SLC3A2 were detected in association with the ~150-kDa complex (Fig. 2B), and co-immunoprecipitation analysis further confirmed the association between SLC7A11, SLC3A2, and OTUB1 after IL-1β stimulation (Fig. 2C)."
OTUB1 affects Proteasome
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3
OTUB1 affects OT5
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2
1
reach
"To justify the cytotoxic and apoptosis effect, the in silico results of OT5 compounds showed that the main interactions between OT5 and OTUB1 are with amino acids in a region considered as potential therapeutic target (active site) (3,5,6) (Figures 3 and 4) that could regulate the c‑Maf axis to generate apoptosis (12) (13)."
sparser
"To justify the cytotoxic and apoptosis effect, the in silico results of OT5 compounds showed that the main interactions between OT5 and OTUB1 are with amino acids in a region considered as potential therapeutic target (active site) (3,5,6) ( xref and xref ) that could regulate the c‑Maf axis to generate apoptosis (12) (13)."
OTUB1 affects Multiple Sclerosis
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3
OTUB1 affects Multiple Myeloma
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3
reach
"Since OTUB1-competent BMDCs showed stronger activation of TAK1 and production of the cytokines IL-12, TNF, and IL-6 upon engagement of TLR2, TLR7, TLR9, and IL-1R, all of which signal via MyD88, and upon TNF stimulation and poly I:C-induced TLR3 activation, both of which induce MyD88-independent signaling, OTUB1 may contribute to proinflammatory DC responses in a wide range of infections and inflammatory disorders."
OTUB1 affects LINC00857
|
3
reach
"OTUB1 has been reported to enhance membrane localization and promote the activation of wild-type KRAS—but not KRAS mutants—by suppressing the enzymatic activity of E2 enzymes ubiquitin-conjugating enzyme 13 (UBC13) and ubiquitin-conjugating enzyme E2 D3 (UBE2D3), indicating that OTUB1 regulates wild-type KRAS in an indirect manner ."
OTUB1 affects K48-Ub 2
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3
OTUB1 affects Interferon
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3
OTUB1 affects Infections
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3
sparser
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
reach
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
OTUB1 affects FIH
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3
reach
"Collectively, these data suggest that OTUB1 facilitates hypoxia adaptation, which might benefit cancer progression.In order to determine whether the formation of FIH and OTUB1 heterodimers could affect OTUB1’s regulation on hypoxia signaling, we used FG4592 to stabilize HIF-1α under normoxia."
OTUB1 affects EN523
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3
OTUB1 affects DNA damage checkpoint signaling
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3
OTUB1 affects Central Nervous System
|
3
OTUB1 affects 17beta-estradiol
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3
OT5 affects OTUB1
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2
1
reach
"To justify the cytotoxic and apoptosis effect, the in silico results of OT5 compounds showed that the main interactions between OT5 and OTUB1 are with amino acids in a region considered as potential therapeutic target (active site) (3,5,6) (Figures 3 and 4) that could regulate the c‑Maf axis to generate apoptosis (12) (13)."
sparser
"To justify the cytotoxic and apoptosis effect, the in silico results of OT5 compounds showed that the main interactions between OT5 and OTUB1 are with amino acids in a region considered as potential therapeutic target (active site) (3,5,6) ( xref and xref ) that could regulate the c‑Maf axis to generate apoptosis (12) (13)."
LINC00857 affects OTUB1
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3
K48-Ub 2 affects OTUB1
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3
sparser
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
reach
"Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays."
FOXM1 over-expression affects OTUB1
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3
EN523 affects OTUB1
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3
sparser
"By the same method, to avoid the issue that
decreased SLC7A11 protein levels are the only factor for the decrease of the OTUB1-SLC7A11 interaction in CD44 knockdown cells
(Input: lane 1 vs. lane 2, xref ), we normalized the amounts of SLC7A11 after
immunoprecipitation (IP: lane 3 vs. lane 4, xref )."
P97 affects OTUB1
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2
Hsa-miR-542-3p affects OTUB1
2
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Glutathione affects OTUB1
1
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1
Endoplasmic reticulum affects OTUB1
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2
CircSEC24B affects OTUB1
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2
Chlorpyrifos affects OTUB1
2
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reach
"The deubiquitinating enzyme ubiquitin aldehyde binding 1 (OTUB1) directly binds to tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits its lysine 63-linked polyubiquitination, thereby inhibiting the activation of ASK1 and its downstream MAPK pathway 73.The ubiquitin system also plays an important role in the activation of other pathways."
OTUB1 affects wound healing
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2
OTUB1 affects ubiquitination degradation FOXM1 breast cancer
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2
OTUB1 affects transcriptional HSF1
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2
OTUB1 affects protein stability HSF1
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2
OTUB1 affects poly-ubiquitin chains
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2
OTUB1 affects pathway
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2
OTUB1 affects p97
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2
OTUB1 affects p53S46P
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2
OTUB1 affects oxaliplatin
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2
OTUB1 affects mineralization
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2
OTUB1 affects migration
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2
OTUB1 affects miR-542-3p
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2
OTUB1 affects glutathione
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2
OTUB1 affects function
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2
OTUB1 affects formation
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2
OTUB1 affects doxorubicin
|
2
reach
"We also identified the correlation between the OTUB1/β-catenin/necroptosis axis and chemotherapy response in BLCA, demonstrating that elevated OTUB1 promotes cisplatin resistance, which is reversed by XAV-939 application.In conclusion, our study unveils the oncogenic role of OTUB1 in BLCA and integrates the complex relationship among OTUB1, BLCA, β-catenin, and necroptosis."
OTUB1 affects circSEC24B
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2
OTUB1 affects cell growth
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2
OTUB1 affects cell differentiation
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2
OTUB1 affects c-Maf polyubiquitination
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2
OTUB1 affects autoubiquitination UBE2E1
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2
OTUB1 affects activation
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2
OTUB1 affects RT4 cells
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2
OTUB1 affects R-SMAD SMAD4 complex
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2
OTUB1 affects Protein Stability
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2
OTUB1 activates Protein Stability. 2 / 2
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2
OTUB1 affects IH
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2
OTUB1 affects E3_Ub_ligase
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1
1
OTUB1 inhibits E3_Ub_ligase. 2 / 2
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1
1
OTUB1 affects E2~Ub
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2
OTUB1 affects Dendritic Cells
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2
OTUB1 affects Circ-BGN
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2
OTUB1 affects Carcinoma, Renal Cell
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1
1
sparser
"As positive control for nuclear localization, CFP-OTU1 was coexpressed with mRFP fused to a bipartite-type nuclear localization signal (NLS) derived from the Agrobacterium VirD2 protein ( xref ). xref B shows that, similarly to free mRFP, CFP-OTU1 accumulated in the cytoplasm—displaying transvacuolar strands (green arrowhead) and variations in cytosol thickness at the cell cortex ( xref , xref )—and in the nucleus (white arrowhead), colocalizing with mRFP-VirD2 NLS."
sparser
"We cannot rule out that at least some of the cytoplasmic signal of CFP-OTU1 derives from degradation of this fusion protein; however, usually, degradation of GFP-tagged proteins results in the loss of fluorescence, representing the rationale for degradation assays that utilize GFP fusions of the proteins of interest ( xref , xref , xref )."
OTUB1 affects 4T1
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2
OTUB1 affects (-)-drimenol synthase
|
2
NPs affects OTUB1
|
2
reach
"Specifically, by inhibiting the activation of OTUB1 deubiquitination, ZnCM NPs could promote CCL5 degradation to induce tDCs and further inhibit the T-cell response, exhibiting Zn homeostasis regulation by ZnCM NPs in RA.In addition, it was shown that the expression of CCL5 was closely related to the activation of NF-κB signalling, leading to regulatory effects on cell fate [60]."
reach
"Collectively, the data above demonstrated that ZnCM NPs could inhibit the activation of OTUB1 deubiquitination, thereby promoting CCL5 degradation via NF-κB signalling to induce tDCs for further T-cell response inhibition, which explained the molecular mechanisms of Zn homeostasis regulation by ZnCM NPs to treat RA."
IFN-I affects OTUB1
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2
Erianin affects OTUB1
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2
E2~Ub affects OTUB1
|
2
DOA1 affects Cdc48
|
2
Circ-BGN affects OTUB1
|
2
reach
"Similar results were also observed in siRNA-mediated knockdown of cathepsin K. Cathepsin K siRNA decreased Raptor protein expression and phosphorylation of OTUB1 and Src in Caki-1 (renal carcinoma), A549 (lung carcinoma), and DU145 (prostate carcinoma) cells, significantly (Fig. 1B)."
reach
"Moreover, inhibition of cathepsin K (by ODN and siRNA) significantly increased SHP2 phosphorylation at Y542, and SHP2 inhibition (by using pharmacological inhibitor and siRNA) interrupted the ODN-mediated dephosphorylation of OTUB1 and Src, eventually stabilizing Raptor (Fig. 2C–F)."
sparser
"As positive control for nuclear localization, CFP-OTU1 was coexpressed with mRFP fused to a bipartite-type nuclear localization signal (NLS) derived from the Agrobacterium VirD2 protein ( xref ). xref B shows that, similarly to free mRFP, CFP-OTU1 accumulated in the cytoplasm—displaying transvacuolar strands (green arrowhead) and variations in cytosol thickness at the cell cortex ( xref , xref )—and in the nucleus (white arrowhead), colocalizing with mRFP-VirD2 NLS."
sparser
"We cannot rule out that at least some of the cytoplasmic signal of CFP-OTU1 derives from degradation of this fusion protein; however, usually, degradation of GFP-tagged proteins results in the loss of fluorescence, representing the rationale for degradation assays that utilize GFP fusions of the proteins of interest ( xref , xref , xref )."
AM146 affects OTUB1
|
2
ACTN1 affects ANXA3, CANX, CNN2, CTNNB1, CTPS1, EPRS1, GLO1, GPI, HMGB1, ITGB1, MAPK1, MAPK3, MYH9, MYO1E, OTUB1, PRDX3, PSMA2, PSMB6, PSME2, RPL22, RPS19, RPS24, SAMHD1, SEC61A1, SYNCRIP, TCAF2, and TPM1
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2
MYH9 binds ACTN1, CANX, GPI, TPM1, EPRS1, ITGB1, ANXA3, CNN2, MAPK1, PSME2, CTPS1, OTUB1, PSMB6, HMGB1, RPS19, SEC61A1, CTNNB1, GLO1, RPL22, PSMA2, SYNCRIP, PRDX3, SAMHD1, TCAF2, MAPK3, RPS24, and MYO1E. 2 / 2
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2
sparser
"However, MYH9, ACTN1, CANX, GPI, TPM1, EPRS, ITGB1, ANXA3, CNN2, MAPK1, PSME2, CTPS1, OTUB1, PSMB6, HMGB1, RPS19, SEC61A1, CTNNB1, GLO1, RPL22, PSMA2, SYNCRIP, PRDX3, SAMHD1, TCAF2, MAPK3, RPS24, and MYO1E, which are associated with immunity, were more highly expressed by SCID mAdMSCs compared with those of C57BL/6 mAdMSCs."
sparser
"MYH9, ACTN1, CANX, GPI, TPM1, EPRS, ITGB1, ANXA3, CNN2, MAPK1, PSME2, CTPS1, OTUB1, PSMB6, HMGB1, RPS19, SEC61A1, CTNNB1, GLO1, RPL22, PSMA2, SYNCRIP, PRDX3, SAMHD1, TCAF2, MAPK3, RPS24, and MYO1E, which are associated with immunity, were expressed at higher levels by the SCID mAdMSCs compared with the C57BL/6 mAdMSCs."
4,4'-sulfonyldiphenol affects OTUB1
2
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