IndraLab
Statements
reach
"The direct interaction of OTUD5 and GPX4 was further confirmed by GST‐pull down, surface plasmon resonance (SPR) and microscale thermophoresis (MST) (Figure 4B,C; Figure S5E, Supporting Information), and the colocalization of OTUD5 and GPX4 proteins in the NRCMs was verified by immunofluorescence (Figure 4D)."
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"As OTUD5 belongs to the DUBs family and plays a critical role in controlling the Ub‐dependent degradation of various proteins, 4‐HNE may reduce the interaction between OTUD5 and GPX4 to promote GPX4 ubiquitination and subsequent degradation.To test whether OTUD5 affects the protein stability of GPX4, we co‐transfected GPX4 with Flag‐OTUD5 or its enzyme‐inactive mutant C224S into HEK293T cells."
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"Taken together, OTUD5 specifically deubiquitinated and stabilized the protein level of GPX4.Furthermore, we confirmed that GPX4 and OTUD5 could form a complex through reciprocal coimmunoprecipitation, immunofluorescence, duolink proximity ligation in situ assay (PLA), and GST‐pull down assay, and that 4‐HNE could weak this binding (Figure
5A–D; Figure S6E, Supporting Information)."
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"We used the database to predict potential ubiquitination‐related enzymes targeting GPX4 (Figure S5A, Supporting Information) and found that E3 ligases MIB2, NEDD4L, STUB1, and deubiquitinase OTUD5 could bind to GPX4 in co‐immunoprecipitation experiments (Figure S5B, Supporting Information)."
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"N‐acetyl cysteine (NAC), an analog of cysteine that competitively binds to 4‐HNE, and amino acid substitution rescued 4‐HNE‐induced cysteine carbonylation of GPX4 and OTUD5, recovered the interaction between GPX4 and OTUD5, alleviated ubiquitination‐dependent degradation of GPX4, and inhibited myocyte ferroptosis."
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"OTUD5 mediates GPX4 deubiquitination to regulate its stability.Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth.Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer.OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD."
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"Therefore, identifying proteins that regulate GPX4 degradation is imperative for promoting ferroptosis without leading to the total elimination of GPX4.Next, we examined whether OTUD5 mediates the deubiquitination of GPX4 and found that overexpression of OTUD5 led to a significant reduction of GPX4 polyubiquitination (Figure 2J,K)."
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"OTUD5 increased GPX4 protein levels and decreased GPX4 ubiquitination in a dose‐dependent manner, whereas ectopic expression of OTUD5 did not affect GPX4 (Figure 4E,F; Figure S5E, Supporting Information), indicating that OTUD5 enzyme activity is indispensable for GPX4 protein stabilization."
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"OTU deubiquitinase 5 (OTUD5), a protein that interacts with GPX4, can promote ferroptosis resistance during ischemia/reperfusion injury by stabilizing GPX4 expression; in turn, hypoxia/ischemia-induced OTUD5 autophagy can destabilize GPX4, leading to ferroptosis-dependent kidney injury (96)."
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"OTUD5 increased GPX4 protein levels and decreased GPX4 ubiquitination in a dose‐dependent manner, whereas ectopic expression of OTUD5 did not affect GPX4 (Figure 4E,F; Figure S5E, Supporting Information), indicating that OTUD5 enzyme activity is indispensable for GPX4 protein stabilization."
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"Notably, OTUD5 overexpression, knockdown or knockout did not impact the mRNA levels of GPX4 (Figure S1A–C), indicating that OTUD5 upregulates GPX4 expression independently of transcriptional level in gastric cancer cells.Subsequently, we determined the regulation of OTUD5 on the half‐life of GPX4."
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"As OTUD5 belongs to the DUBs family and plays a critical role in controlling the Ub‐dependent degradation of various proteins, 4‐HNE may reduce the interaction between OTUD5 and GPX4 to promote GPX4 ubiquitination and subsequent degradation.To test whether OTUD5 affects the protein stability of GPX4, we co‐transfected GPX4 with Flag‐OTUD5 or its enzyme‐inactive mutant C224S into HEK293T cells."
OTUD5 is modified
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OTUD5 is phosphorylated.
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"The phosphorylated DUBA displays essentially the same predicted secondary structure, which is in good agreement with the crystal structures of both non-phosphorylated DUBA in free form (PDB ID: 3PFY) and phosphorylated DUBA covalently linked to ubiquitin aldehyde (PDB ID: 3TMP)."
sparser
"A nuclear magnetic resonance (NMR) analysis revealed that the phosphorylation of Ser177 alone does not induce significant structural changes, and only after binding ubiquitin does Ser177-phosphorylated OTUD5 show significant structural changes that activate its enzymatic activity."
OTUD5 is ubiquitinated.
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"Using TUBE2 (tandem ubiquitin-binding entity 2), which serves as a pan-ubiquitin chain binder when four repeats of the UBA1 domains from HR23A are tandemly fused xref , we found that OTUD5 pan-ubiquitylation was enhanced by the expression of wild-type, but not catalytically inactive (C1959A), TRIP12 (Fig. xref )."
OTUD5 is produced.
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"The data on a catalytically-inactive OTUD5 (Fig. xref ) suggest that the ubiquitylation of OTUD5 by TRIP12 and UBR5 appears as if they act sequentially because OTUD5 DUB activity negates UBR5 activity, which is different from typical chain initiation (priming)-elongation model xref , xref ."
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"Indeed, the blockade of DUBA-mediated deubiquitination of TRAF3 by DUBA-specific siRNA cancelled the negative regulatory effects of NOD2 on DSS-induced colitis in mice treated with CpG, and mice treated with DUBA-siRNA displayed severe DSS-induced colitis even after repeated MDP injections (67, 68)."
sparser
"The data presented thus far indicate that OTUD5 is cooperatively modified by K29-specific TRIP12 and K48-specific UBR5, resulting in the conjugation of K29/K48-linked branched ubiquitin chains, and the biological importance of TRIP12–OTUD5 antagonism is observed in TNF-α–induced NF-κB signaling."
sparser
"This equilibrium favors ubiquitin chain assembly and subsequent OTUD5 degradation when TRIP12 interacts with OTUD5; UBR5 assembles K48-linked ubiquitin chains onto previously formed K29-linked chains more efficiently than de novo ubiquitylation (Fig. xref ), presumably through ubiquitin interaction of the UBA domain (Fig. xref and ref. xref )."
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"Using TUBE2 (tandem ubiquitin-binding entity 2), which serves as a pan-ubiquitin chain binder when four repeats of the UBA1 domains from HR23A are tandemly fused , we found that OTUD5 pan-ubiquitylation was enhanced by the expression of wild-type, but not catalytically inactive (C1959A), TRIP12 (Fig. 1f)."
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"The data on a catalytically-inactive OTUD5 (Fig. xref ) suggest that the ubiquitylation of OTUD5 by TRIP12 and UBR5 appears as if they act sequentially because OTUD5 DUB activity negates UBR5 activity, which is different from typical chain initiation (priming)-elongation model xref , xref ."
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"Because UBR5 appears to stably associate with OTUD5 , and because TRIP12 possesses phosphorylation sites (https://www.phosphosite.org), we presume that TRIP12 may associate with OTUD5 under certain cellular conditions, triggering rapid OTUD5 degradation to fulfill cellular demand.Second, our model suggests complex ubiquitin architectures consisting of K29 and K48 linkages."
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"42
To validate our hypothesis that OTUD5 may recruit NEDD4 to degrade α‐Syn, we first demonstrated that OTUD5 failed to enhance the degradation of α‐Syn when NEDD4 was knockdown, while NEDD4 overexpression promoted the degradation of α‐Syn induced by OTUD5, which indicated that OTUD5 mediated α‐Syn degradation relying on NEDD4."
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"Mechanically, we found that OTUD5 deficiency further reduced endogenous K63‐linked polyubiquitination of α‐Syn and upregulated its protein level, then promoted the formation of pathologic p‐α‐Syn and aggravated the pathogenic consequences induced by α‐Syn PFF.In summary, we demonstrated that OTUD5 negatively regulated α‐Syn protein levels by promoting endolysosomal degradation independent of its deubiquitinate activity."
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"Mechanically, we found that OTUD5 deficiency further reduced endogenous K63‐linked polyubiquitination of α‐Syn and upregulated its protein level, then promoted the formation of pathologic p‐α‐Syn and aggravated the pathogenic consequences induced by α‐Syn PFF.In summary, we demonstrated that OTUD5 negatively regulated α‐Syn protein levels by promoting endolysosomal degradation independent of its deubiquitinate activity."
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"To study the cellular consequence of specifically blocking the interaction between OTUD5 and FACT (OTUD5 overexpression or complete knockout causes aberration in cell cycle and apoptosis), we generated a HeLa knock-in (KI) cell line in which the D537A mutation is introduced into the genomic loci of OTUD5 (OTUD5 ) using the CRISPR-Cas9 method (Supplementary Figure S2; sequencing information of 4 clones)."
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"Thus, our work propose that FACT is an important factor in this in cis regulation, and that FACT is subject to regulation by OTUD5–UBR5 complex for the non-lesion stalling of Pol II.Our work leaves several open-ended questions; our data collectively suggest that OTUD5 and UBR5 repress FACT histone exchange activity, but how does this complex exactly achieve this?"
OTUD5 affects DBC1
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"The direct interaction of OTUD5 and GPX4 was further confirmed by GST‐pull down, surface plasmon resonance (SPR) and microscale thermophoresis (MST) (Figure 4B,C; Figure S5E, Supporting Information), and the colocalization of OTUD5 and GPX4 proteins in the NRCMs was verified by immunofluorescence (Figure 4D)."
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"As OTUD5 belongs to the DUBs family and plays a critical role in controlling the Ub‐dependent degradation of various proteins, 4‐HNE may reduce the interaction between OTUD5 and GPX4 to promote GPX4 ubiquitination and subsequent degradation.To test whether OTUD5 affects the protein stability of GPX4, we co‐transfected GPX4 with Flag‐OTUD5 or its enzyme‐inactive mutant C224S into HEK293T cells."
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"Taken together, OTUD5 specifically deubiquitinated and stabilized the protein level of GPX4.Furthermore, we confirmed that GPX4 and OTUD5 could form a complex through reciprocal coimmunoprecipitation, immunofluorescence, duolink proximity ligation in situ assay (PLA), and GST‐pull down assay, and that 4‐HNE could weak this binding (Figure
5A–D; Figure S6E, Supporting Information)."
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"We used the database to predict potential ubiquitination‐related enzymes targeting GPX4 (Figure S5A, Supporting Information) and found that E3 ligases MIB2, NEDD4L, STUB1, and deubiquitinase OTUD5 could bind to GPX4 in co‐immunoprecipitation experiments (Figure S5B, Supporting Information)."
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"N‐acetyl cysteine (NAC), an analog of cysteine that competitively binds to 4‐HNE, and amino acid substitution rescued 4‐HNE‐induced cysteine carbonylation of GPX4 and OTUD5, recovered the interaction between GPX4 and OTUD5, alleviated ubiquitination‐dependent degradation of GPX4, and inhibited myocyte ferroptosis."
DBC1 affects OTUD5
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OTUD5 affects cell population proliferation
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OTUD5 activates cell population proliferation.
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OTUD5 activates cell population proliferation. 10 / 11
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"Collectively, these results imply that OTUD5 orchestrates ferroptosis in gastric cancer cells.Moreover, we evaluated the impact of OTUD5 knockout on the cell cycle of gastric cancer cells by an EdU incorporation assay, and the results revealed that OTUD5 depletion decreased the proportion of cells in S phase, indicating impaired cell proliferation (Figure 3M,N)."
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"We treated control and OTUD5‐KO cells with nutlin‐3a and observed that knockout of OTUD5, in combination with nutlin‐3a treatment, led to a reduction in protein levels of OTUD5 and GPX4 (Figure 5A,B), thereby triggering ferroptosis in cancer cells and consequently inhibiting cell proliferation (Figure 5C,D)."
OTUD5 inhibits cell population proliferation.
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OTUD5 inhibits cell population proliferation. 9 / 9
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"We treated control and OTUD5‐KO cells with nutlin‐3a and observed that knockout of OTUD5, in combination with nutlin‐3a treatment, led to a reduction in protein levels of OTUD5 and GPX4 (Figure 5A,B), thereby triggering ferroptosis in cancer cells and consequently inhibiting cell proliferation (Figure 5C,D)."
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"To study the cellular consequence of specifically blocking the interaction between OTUD5 and FACT (OTUD5 overexpression or complete knockout causes aberration in cell cycle and apoptosis), we generated a HeLa knock-in (KI) cell line in which the D537A mutation is introduced into the genomic loci of OTUD5 (OTUD5 ) using the CRISPR-Cas9 method (Supplementary Figure S2; sequencing information of 4 clones)."
OTUD5 affects Interferon
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OTUD5 inhibits Interferon.
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OTUD5 activates Interferon.
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OTUD5 deubiquitinates Interferon.
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OTUD5 affects NP
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"Motions in the apo state of enzymes can facilitate substrate binding by enabling transitions into to a binding competent state xref , xref and can also regulate the catalytic cycle by allowing access to conformational states conducive for catalytic turnover. xref – xref The low activity of np-DUBA likely results from its inability to form a highly productive enzyme-substrate complex rather than low binding affinity to substrates because only 3-fold enhancement in the affinity to the fluorogenic ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) substrate was observed upon phosphorylation, whereas the enhancement in k cat is 300-fold. xref We can speculate that an important feature of the productive enzyme-substrate complex is that the α1 helix can adopt a closed conformation, as defined by the crystal structure of p-DUBA in the ubiquitin-bound state. xref The only conformer in np-DUBA lies between the a and b conformers in terms of structural characteristics according to the relative positions of cross-peaks. xref This observation indicates that at least in the free state, the α1 helix in np-DUBA adopts a more open conformation than the a conformer in p-DUBA."
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"Broadening of NMR spectral lines and the resulting low signal intensities are signatures of conformational exchanges on the μs-ms scales. xref Among ~ 120 cross-peaks detectable in the 15 N TROSY spectra of p-DUBA, many display broad 1 H lines, whereas the 15 N transverse relaxation rates of majority of the resonances are consistent with the molecular weight. xref , xref TROSY spectra of nonphosphorylated DUBA (np-DUBA) display similar features."
sparser
"The data were subsequently group fit with a common exchange rate for residues that satisfy χ 2 group /χ 2 invididual < 2.0. xref Group fitting yielded k ex = 4954 ± 82 s −1 for p-DUBA ( xref ). np-DUBA undergoes a similar conformational exchange process with the exchange rate of 5750 ± 110 s −1 ( xref )."
Phosphatase affects OTUD5
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OTUD5 affects ferroptosis
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OTUD5 inhibits ferroptosis.
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OTUD5 inhibits ferroptosis. 10 / 10
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"We treated control and OTUD5‐KO cells with nutlin‐3a and observed that knockout of OTUD5, in combination with nutlin‐3a treatment, led to a reduction in protein levels of OTUD5 and GPX4 (Figure 5A,B), thereby triggering ferroptosis in cancer cells and consequently inhibiting cell proliferation (Figure 5C,D)."
OTUD5 activates ferroptosis.
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"The data presented thus far indicate that OTUD5 is cooperatively modified by K29-specific TRIP12 and K48-specific UBR5, resulting in the conjugation of K29/K48-linked branched ubiquitin chains, and the biological importance of TRIP12–OTUD5 antagonism is observed in TNF-α–induced NF-κB signaling."
sparser
"This equilibrium favors ubiquitin chain assembly and subsequent OTUD5 degradation when TRIP12 interacts with OTUD5; UBR5 assembles K48-linked ubiquitin chains onto previously formed K29-linked chains more efficiently than de novo ubiquitylation (Fig. xref ), presumably through ubiquitin interaction of the UBA domain (Fig. xref and ref. xref )."
sparser
"To validate which type of MyD88 polyubiquitin chain was abrogated by OTUD5, HA-ubiquitin mutants K0, K6, K11, K27, K29, K33, K48 and K63 (containing only one lysine residue with other lysine residues replaced by arginine), together with Myc-MyD88 and Flag-OTUD5 (WT) were co-transfected into HEK293T cells."
sparser
"The crystal structure of the Ub-aldehyde complex with phosphorylated OTUD5 reveals a remarkable interaction between the phosphorylated Ser177 of OTUD5 and the guanidinium moiety of Arg74 of the bound ubiquitin showing that the phosphorylation is essential for the DUB activity [ xref ]."
sparser
"In the crystal structure of the Ser177-phosphorylated form of OTUD5 bound with ubiquitin ( xref ), the phosphate group has intramolecular interactions with other OTUD5 polar residues (including Arg272), and also has intermolecular interactions with the C-terminal tail of the bound ubiquitin, precisely orienting its C-terminus for catalysis."
sparser
"The crystal structure of the Ub-aldehyde complex with phosphorylated OTUD5 reveals a remarkable interaction between the phosphorylated Ser177 of OTUD5 and the guanidinium moiety of Arg74 of the bound ubiquitin showing that the phosphorylation is essential for the DUB activity [ xref ]."
sparser
"In the crystal structure of the Ser177-phosphorylated form of OTUD5 bound with ubiquitin ( xref ), the phosphate group has intramolecular interactions with other OTUD5 polar residues (including Arg272), and also has intermolecular interactions with the C-terminal tail of the bound ubiquitin, precisely orienting its C-terminus for catalysis."
OTUD5 affects DNA-templated transcription
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OTUD5 activates DNA-templated transcription.
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OTUD5 activates DNA-templated transcription. 6 / 6
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"Using the ROC curve and Kaplan–Meier method, OTUD5 was demonstrated as an interesting biomarker for predicting HBeAg seroconversion.In summary, we revealed that deubiquitinase OTUD5 could positively regulate HBV transcription and replication in HepG2.2.15 cells by deubiquitinating the K48-mediated ubiquitination of hepatitis B precore/core components to promote HBV infection."
OTUD5 inhibits DNA-templated transcription.
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OTUD5 inhibits DNA-templated transcription. 2 / 2
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"OTUD5 downregulates the stability of the transcription factor RORγt, which induces IL-17 production in T cells, and interestingly, it does so indirectly by stabilizing UBR5 (43); the model suggested that UBR5 ubiquitinates and degrades RORγt. Therefore, the role of OTUD5 in cytokine production has a similarity with the role described herein, in that it negatively impacts transcription, at least in part through UBR5 stabilization."
OTUD5 affects cell growth
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OTUD5 inhibits cell growth.
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OTUD5 activates cell growth.
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OTUD5 activates cell growth. 1 / 1
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"This suggests the possibility that OTUD5 is directly phosphorylated by ATM to function as an amplifier of ATM-dependent DDR signaling in a potential positive-feedback circuit, resembling its role in mTOR signaling.In the context of DNA repair, OTUD5 has been suggested to promote NHEJ by counteracting the degradation of Ku80, a core NHEJ factor, in certain cell lines ."
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"This shows that the residual ATM activity in OTUD5-deficient cells is inadequate to support sufficient phosphorylation of KAP1 , a key step in DNA repair in KAP1-rich genomic environments such as the telomeres and heterochromatin, thereby translating into a repair defect specifically in these regions."
OTUD5 affects IFN-I
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"Indeed, we found OTUD5 to promote ATM-dependent DDR signaling in a manner that is epistatic with UBR5, dependent on its catalytic activity and involving ATMIN, supporting that OTUD5 acts via UBR5.Early biochemical studies performed on OTUD5 suggested that phosphorylation at residue Ser-177 is vital for its DUB activity in vitro ."
OTUD5 affects innate immune response
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OTUD5 inhibits innate immune response.
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OTUD5 inhibits innate immune response. 5 / 5
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"Also known as DUBA (deubiquitinating enzyme A), the OTUD5 protein was shown to suppress type-I interferon (IFN-I) dependent innate immune response, by cleaving the poly-ubiquitin chain from the IFN-I adaptor protein, thus causing the disassociation of the adaptor from the downstream signaling complex, and ultimately the interruption of the IFN-I signaling cascade."
OTUD5 activates innate immune response.
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OTUD5 activates innate immune response. 1 / 1
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OTUD5 affects apoptotic process
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OTUD5 activates apoptotic process.
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OTUD5 activates apoptotic process. 4 / 4
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"To study the cellular consequence of specifically blocking the interaction between OTUD5 and FACT (OTUD5 overexpression or complete knockout causes aberration in cell cycle and apoptosis), we generated a HeLa knock-in (KI) cell line in which the D537A mutation is introduced into the genomic loci of OTUD5 (OTUD5 ) using the CRISPR-Cas9 method (Supplementary Figure S2; sequencing information of 4 clones)."
OTUD5 inhibits apoptotic process.
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"We further detected the protein levels of PTEN in A549 and HCI-H460 cells with another Western blot assay and uncovered that overexpression of OTUD5 promoted the protein level of PTEN, while PTEN protein levels were further increased on treatment with MG132 (a proteasome inhibitor) (p < 0.05, Figure 3C), indicating that OTUD5 may regulate PTEN expression through the proteasome pathway."
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"Nevertheless, whether miR-652-3p regulates that the OTUD5/PTEN axis has not been discussed before and warrants further exploration.In light of the abovementioned evidence, we put forth a hypothesis that OTUD5 deubiquitinates and stabilizes PTEN to suppress NSCLC cell proliferation, invasion, and migration, whereas this mechanism could be counteracted by miR-652-3p overexpression."
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"The obtained findings revealed that OTUD5 deubiquitinated and stabilized PTEN to suppress NSCLC proliferation, invasion, and migration, and miR-652-3p serving as an upstream target of OTUD5 abolished the tumor-suppressing role of OTUD5/PTEN in NSCLC.There is a plethora of evidence to highlight the correlation between decreased levels of OTUD5 and poor prognoses in NSCLC patients, such that OTUD5 knockdown exerts an enhancing effect on NSCLC cell proliferation, migration, and chemoresistance [13]."
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"Subsequent experimentation revealed that miR-652-3p inhibition brought about an increase in OTUD5 expression levels (p < 0.05, Figure 6B and C) and PTEN protein levels (p < 0.05, Figure 6D and E), while simultaneously reducing the ubiquitination level of PTEN, cell viability (p < 0.05, Figure 6F), and the number of migrated and invaded cells (p < 0.05, Figure 6G and H)."
OTUD5 increases the amount of OTUD5.
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OTUD5 decreases the amount of OTUD5.
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"Altogether, the abovementioned findings and valuable evidence highlighted that OTUD5 exerts an anti-tumor function by means of deubiquitinating and stabilizing PTEN, while enhancing the ubiquitination of PTEN reverses the inhibition of OTUD5 overexpression on NSCLC progression.Furthermore, we focused our efforts on the upstream targets of OTUD5."
OTUD5 deubiquitinates OTUD5.
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OTUD5 activates OTUD5.
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OTUD5 affects inflammatory response
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OTUD5 affects immune response
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OTUD5 affects cell differentiation
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OTUD5 activates cell differentiation.
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OTUD5 activates cell differentiation. 3 / 3
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"Previous research has demonstrated that the ability of OTUD5 to cleave K48‐ubiquitin chains is required to support differentiation and that, during embryonic development, OTUD5 regulates cell fate decisions by cleaving the degrading K48‐ubiquitin junctions of a substrate (Beck et al., 2021; Park et al., 2015; Yin et al., 2019)."
OTUD5 inhibits cell differentiation.
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OTUD5 affects DNA repair
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OTUD5 activates DNA repair. 5 / 5
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"Taken together, we conclude that OTUD5 is required both for efficient NHEJ and for efficient MMEJ at deprotected telomeres.Having established that OTUD5 promotes DNA repair by NHEJ and MMEJ at telomeres, we assessed if the role of OTUD5 in DNA repair extends beyond a telomeric context, especially since we found OTUD5 to promote both telomere-specific and genome-wide DDR activation in mouse and human cells."
reach
"Indeed, we found OTUD5 to promote ATM-dependent DDR signaling in a manner that is epistatic with UBR5, dependent on its catalytic activity and involving ATMIN, supporting that OTUD5 acts via UBR5.Early biochemical studies performed on OTUD5 suggested that phosphorylation at residue Ser-177 is vital for its DUB activity in vitro ."
OTUD5 affects TNF-α production
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"Taken together, these findings revealed that OTUD5 stimulates TLR/IL-1R-mediated production of proinflammatory cytokines.Since TLR/IL-1R-mediated activation of NF-κB and MAPKs lead to the production of inflammatory cytokines [45, 46], we next explored the role of OTUD5 in the NF-κB and MAPK signaling pathways by transfecting Otud5-siRNA into PMs."
OTUD5 affects Neoplasm Invasiveness
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OTUD5 inhibits Neoplasm Invasiveness.
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OTUD5 activates Neoplasm Invasiveness.
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OTUD5 activates Neoplasm Invasiveness. 1 / 1
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OTUD5 affects NSCLC
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OTUD5 affects signal transduction
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OTUD5 inhibits signal transduction.
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OTUD5 inhibits signal transduction. 2 / 2
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"Using an inhibitor of ERK1/2, we demonstrated OTUD5 inhibited ERK1/2 MAPK signaling pathway to accumulate HNF4α expression to benefit HBV replication.In this study, the healthy cohort, HBV carriers and chronic hepatitis B patients were enrolled, the expression OTUD5 in different groups was analyzed, and significant differences of OTUD5 were observed between the HBV-negative cohort and HBV positive carriers, meaning the expression of OTUD5 in human serum was promoted by infecting hepatitis B virus."
OTUD5 activates signal transduction.
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OTUD5 activates signal transduction. 1 / 1
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OTUD5 affects polyubiquitin chain
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"This suggests the possibility that OTUD5 is directly phosphorylated by ATM to function as an amplifier of ATM-dependent DDR signaling in a potential positive-feedback circuit, resembling its role in mTOR signaling.In the context of DNA repair, OTUD5 has been suggested to promote NHEJ by counteracting the degradation of Ku80, a core NHEJ factor, in certain cell lines ."
OTUD5 affects MAPK cascade
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"Using an inhibitor of ERK1/2, we demonstrated OTUD5 inhibited ERK1/2 MAPK signaling pathway to accumulate HNF4α expression to benefit HBV replication.In this study, the healthy cohort, HBV carriers and chronic hepatitis B patients were enrolled, the expression OTUD5 in different groups was analyzed, and significant differences of OTUD5 were observed between the HBV-negative cohort and HBV positive carriers, meaning the expression of OTUD5 in human serum was promoted by infecting hepatitis B virus."
OTUD5 affects Cell Survival
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OTUD5 activates Cell Survival. 3 / 3
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"Specifically, the role of OTUD5 in stabilizing GPX4 suggests that therapeutic modulation of its activity might be a feasible strategy for controlling GPX4 levels, thus manipulating the course of ferroptosis and ultimately, the progression of AKI.Through a series of experiments, we demonstrate that OTUD5 plays a protective role against ferroptosis and contributes to cell survival."
OTUD5 affects Carcinogenesis
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OTUD5 activates Carcinogenesis.
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OTUD5 activates Carcinogenesis. 2 / 2
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"OTUD5 acts as a tumor inhibitor in non-small cell lung cancer and cervical cancer.36 37 However, OTUD5 promotes carcinogenesis in triple-negative breast cancer and bladder cancer.38 39 Hence, the specific function of OTUD5 in different cancers needs to be analyzed on a case-to-case basis."
OTUD5 inhibits Carcinogenesis.
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OTUD5 inhibits Carcinogenesis. 1 / 1
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"This suggests the possibility that OTUD5 is directly phosphorylated by ATM to function as an amplifier of ATM-dependent DDR signaling in a potential positive-feedback circuit, resembling its role in mTOR signaling.In the context of DNA repair, OTUD5 has been suggested to promote NHEJ by counteracting the degradation of Ku80, a core NHEJ factor, in certain cell lines ."
Type p53 affects OTUD5
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Type p53 increases the amount of OTUD5.
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"OTUD5 mediates GPX4 deubiquitination to regulate its stability.Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth.Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer.OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD."
Type p53 decreases the amount of OTUD5.
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"OTUD5 mediates GPX4 deubiquitination to regulate its stability.Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth.Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer.OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD."
Region affects OTUD5
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Polyubiquitin chains affects OTUD5
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"Using TUBE2 (tandem ubiquitin-binding entity 2), which serves as a pan-ubiquitin chain binder when four repeats of the UBA1 domains from HR23A are tandemly fused xref , we found that OTUD5 pan-ubiquitylation was enhanced by the expression of wild-type, but not catalytically inactive (C1959A), TRIP12 (Fig. xref )."
MiR-652-3p affects OTUD5
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Lipopolysaccharide affects OTUD5
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Doxorubicin affects OTUD5
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Doxorubicin inhibits OTUD5.
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Doxorubicin inhibits OTUD5. 1 / 1
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Doxorubicin activates OTUD5.
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Doxorubicin activates OTUD5. 1 / 1
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"Further supporting the idea that OTUD5 regulates cell fate commitment through stabilizing chromatin remodelers, we observed that OTUD5-regulated neural enhancers were often bound by SMARCA4 ( xref ), a component of the BAF complex recruited by ARID1A/B ( xref ) in neural progenitor cells ( xref )."
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RING domain affects OTUD5
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OTUD5 affects transformation malignant A549 cells
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OTUD5 affects polyubiquitin chains
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OTUD5 affects migration invasion HCC827 cells
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OTUD5 affects migration invasion A549 cells
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OTUD5 affects doxorubicin
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"Consistent with the roles of Fanconi Anemia proteins in CFS stability (50) and limiting aberrant R-loop formations (21,22), depletion of FANCD2 was synthetically lethal with loss of FACT regulation in the OTUD5 cells.A previous study showed that depleting SPT16 increases DNA–RNA hybrids and genomic instability in yeast and human cells (35)."
sparser
"Further supporting the idea that OTUD5 regulates cell fate commitment through stabilizing chromatin remodelers, we observed that OTUD5-regulated neural enhancers were often bound by SMARCA4 ( xref ), a component of the BAF complex recruited by ARID1A/B ( xref ) in neural progenitor cells ( xref )."
| PMC
OTUD5 affects RLH
|
2
OTUD5 affects RING domain
|
2
OTUD5 affects NSCLC cells
|
2
eidos
"* p < .05 , * * p < .01 , and * * * p < .001 [ Colour figure can be viewed at wileyonlinelibrary.com ] OTUD5 impeded the progression of NSCLC cells via regulating p53 In order to study whether OTUD5 regulates p53 expression in NSCLC , OTUD5 siRNA and NC siRNA were transfected into A549 cells , respectively ."
| PMC
OTUD5 affects K63
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2
OTUD5 affects IHC
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2
OTUD5 affects IFN-1
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2
OTUD5 affects Figs
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2
OTUD5 affects E3_Ub_ligase
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2
OTUD5 affects DNA Breaks, Double-Stranded
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2
OTUD5 inhibits DNA Breaks, Double-Stranded. 2 / 2
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2
OTUD5 affects ARID1A/B
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2
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2
OTUD5 inhibits 2,4,6-trinitrobenzenesulfonic acid.
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1
OTUD5 inhibits 2,4,6-trinitrobenzenesulfonic acid. 1 / 1
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1
OTUD5 activates 2,4,6-trinitrobenzenesulfonic acid.
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1
OTUD5 activates 2,4,6-trinitrobenzenesulfonic acid. 1 / 1
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1
K63 affects OTUD5
|
2
reach
"OTU deubiquitinase 5 (OTUD5), a protein that interacts with GPX4, can promote ferroptosis resistance during ischemia/reperfusion injury by stabilizing GPX4 expression; in turn, hypoxia/ischemia-induced OTUD5 autophagy can destabilize GPX4, leading to ferroptosis-dependent kidney injury (96)."
IL-1RI affects OTUD5
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2
ARID1A/B affects OTUD5
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2
Proteasome inhibitor affects OTUD5
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1
Proteasome inhibitor decreases the amount of OTUD5. 1 / 1
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1
Polyubiquitin affects OTUD5
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1
Polyubiquitin chains affects K63
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1
Polyubiquitin chains affects K48
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1
P53 activator affects OTUD5
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1
P53 activator decreases the amount of OTUD5. 1 / 1
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1
reach
"To further investigate the role of ERK1/2 and p38 signaling in OTUD5-mediated promotion of HNF4ɑ or HNF1ɑ, we treated the OTUD5-sh HepG2.2.15 cells with ERK1/2-specific pharmacological inhibitor (PD98059), JNK-specific pharmacological inhibitor (SP600125) and p38-specific pharmacological inhibitor (SB203580), and then tested the effect of OTUD5 on the protein level of HNF1α and HNF4α."
MiR-210 affects OTUD5
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1
Hsa-mir-3149 affects OTUD5
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1
Hsa-mir-144 affects OTUD5
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1
Hsa-mir-137 affects OTUD5
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1
Dapagliflozin affects OTUD5
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1
Dapagliflozin decreases the amount of OTUD5. 1 / 1
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1
TRAF3 affects K63
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1
TRAF-C affects RING domain
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1
TRAF-C region affects RING domain
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1
TAK1-TAB2 affects OTUD5
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1
|
1
Suppressor of Cytokine Signalling 3 activates OTUD5. 1 / 1
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1
Reperfusion Injury affects OTUD5
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1
Reperfusion Injury inhibits OTUD5. 1 / 1
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1
RSL3 affects OTUD5
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1
RING domain affects TRAF-C
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1
RING domain affects TRAF-C region
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1
OTUD5 affects viral transcription
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1
OTUD5 activates viral transcription. 1 / 1
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1
OTUD5 affects viral process
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1
OTUD5 activates viral process. 1 / 1
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1
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1
OTUD5 inhibits tumor necrosis factor production. 1 / 1
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1
OTUD5 affects tumor growth
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1
OTUD5 affects triglyceride
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1
OTUD5 inhibits triglyceride. 1 / 1
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1
OTUD5 affects transcriptional
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1
OTUD5 affects receptor-interacting protein kinase 2
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1
OTUD5 affects radiosensitivity cervical cancer cells
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1
OTUD5 affects proteolysis
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1
OTUD5 inhibits proteolysis. 1 / 1
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1
OTUD5 affects protein SFN
|
1
eidos
"In addition , the ubiquitination level of MAVS was reduced following OTUD5 coexpression , and OTUD5 increased the protein level of SFN , demonstrating that OTUD5 was possibly involved in these signaling pathways to work with the TRIM25 E3 ubiquitin ligase in the protein complex ( Supplementary Fig. 5 ) ."
OTUD5 affects programmed cell death
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1
OTUD5 activates programmed cell death. 1 / 1
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1
OTUD5 affects polyubiquitin
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1
OTUD5 affects physiological role
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1
OTUD5 activates physiological role. 1 / 1
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1
OTUD5 affects nucleosome assembly
|
1
OTUD5 inhibits nucleosome assembly. 1 / 1
|
1
OTUD5 affects miR-210
|
1
OTUD5 affects metastasis cells
|
1
OTUD5 affects metastasis NSCLC cells
|
1
OTUD5 affects malonaldehyde
|
1
OTUD5 increases the amount of malonaldehyde. 1 / 1
|
1
OTUD5 affects maleate(2-)
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1
OTUD5 activates maleate(2-). 1 / 1
|
1
OTUD5 affects mTOR signaling pathway
|
1
OTUD5 affects localization
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1
OTUD5 activates localization. 1 / 1
|
1
OTUD5 affects interleukin-17 production
|
1
OTUD5 inhibits interleukin-17 production. 1 / 1
|
1
OTUD5 affects innate antiviral antitumor immunity
|
1
OTUD5 affects immune responses
|
1
OTUD5 affects histone exchange
|
1
OTUD5 inhibits histone exchange. 1 / 1
|
1
reach
"Thus, our work propose that FACT is an important factor in this in cis regulation, and that FACT is subject to regulation by OTUD5–UBR5 complex for the non-lesion stalling of Pol II.Our work leaves several open-ended questions; our data collectively suggest that OTUD5 and UBR5 repress FACT histone exchange activity, but how does this complex exactly achieve this?"
OTUD5 affects histone deacetylation
|
1
OTUD5 activates histone deacetylation. 1 / 1
|
1
OTUD5 affects hippo signaling
|
1
OTUD5 activates hippo signaling. 1 / 1
|
1
OTUD5 affects glutathione
|
1
OTUD5 activates glutathione. 1 / 1
|
1
OTUD5 affects gene expression
|
1
OTUD5 activates gene expression. 1 / 1
|
1
OTUD5 affects erastin
|
1
OTUD5 affects enrichment TRIM25 PML
|
1
reach
"In addition, genetic deletion of OTUD5 in DA neurons significantly aggravated the α‐Syn PFF‐induced neurodegeneration in vivo, while OTUD5 overexpression rescued the DA neuron damage induced by α‐Syn PFF in vitro.Recent studies emphasized the importance of DUBs in regulating the fate of α‐Syn."
OTUD5 affects dapagliflozin
|
1
OTUD5 inhibits dapagliflozin. 1 / 1
|
1
OTUD5 affects chemoradiotherapy resistance
|
1
eidos
"Since the FACT histone chaperone complex can promote the resistance of tumor cells to DNA damage factors ( Dejmek , Iglehart , & Lazaro , 2009 ; Koman et al ., 2012 ; Yarnell , Oh , Reinberg , & Lippard , 2001 ) , a follow-up research is necessary to determine whether OTUD5 can reduce chemoradiotherapy resistance by antagonizing the FACT histone chaperone complex ."
| PMC
OTUD5 affects accessible chromatin neuroectodermal aberrant
|
1
OTUD5 affects WT
|
1
OTUD5 affects VSV-G pseudotype
|
1
OTUD5 affects UBR5-ATMIN
|
1
|
1
OTUD5 inhibits Triple Negative Breast Neoplasms. 1 / 1
|
1
reach
"OTUD5 acts as a tumor inhibitor in non-small cell lung cancer and cervical cancer.36 37 However, OTUD5 promotes carcinogenesis in triple-negative breast cancer and bladder cancer.38 39 Hence, the specific function of OTUD5 in different cancers needs to be analyzed on a case-to-case basis."
OTUD5 affects Th17
|
1
OTUD5 affects TRAF3-TBK1 interaction
|
1
OTUD5 affects TRAF-C
|
1
OTUD5 affects TRAF-C region
|
1
reach
"Mice lacking IL-1RI signaling fail to produce a protective type I IFN response after administration of TLR9 ligand (CpG), suggesting that regulation of DUBA expression by IL-1 signaling attenuates TLR9-mediated proinflammatory responses.In virus-induced sepsis, the virus triggers a strong inflammatory response by activating the host’s immune system, where overactivation of the type I interferon pathway and the NF-κB signaling pathway often leads to SIRS and cytokine storm (61, 62)."
OTUD5 affects TAK1-TAB2
|
1
OTUD5 affects TAK1-MAPK
|
1
reach
"Collectively, these results imply that OTUD5 orchestrates ferroptosis in gastric cancer cells.Moreover, we evaluated the impact of OTUD5 knockout on the cell cycle of gastric cancer cells by an EdU incorporation assay, and the results revealed that OTUD5 depletion decreased the proportion of cells in S phase, indicating impaired cell proliferation (Figure 3M,N)."
OTUD5 affects RORgammat
|
1
OTUD5 affects RORgammat protein
|
1
OTUD5 affects RNAPII
|
1
OTUD5 affects RNA biosynthetic process
|
1
OTUD5 inhibits RNA biosynthetic process. 1 / 1
|
1
OTUD5 affects RNA Pol II
|
1
OTUD5 affects RING domain, and TRAF-C
|
1
OTUD5 affects RING domain, and TRAF-C region
|
1
OTUD5 affects Parkinson Disease
|
1
OTUD5 activates Parkinson Disease. 1 / 1
|
1
OTUD5 affects PML-NBs
|
1
OTUD5 affects MASH
|
1
reach
"Metabolic tracking revealed that OTUD5 knockdown induced a significantly decreased abundance of tricarboxylic acid (TCA) cycle metabolites (such as M2 citrate, M2 ketoglutarate, M2 succinate, and M2 fumarate), with a compensatory increase in the abundance of glycolytic metabolites (such as M6 G-6-P, M6 F-6-P, M6 F-1, 6-P, M3 pyruvate, and M3 lactate)."
OTUD5 affects K63-linked polyubiquitination AKT
|
1
OTUD5 affects K48
|
1
OTUD5 affects Inflammatory Bowel Disease
|
1
OTUD5 binds Inflammatory Bowel Disease. 1 / 1
|
1
OTUD5 affects Hypertrophy
|
1
OTUD5 inhibits Hypertrophy. 1 / 1
|
1
OTUD5 affects HDAC1/2
|
1
OTUD5 affects HBc
|
1
OTUD5 affects DNA damage response
|
1
OTUD5 activates DNA damage response. 1 / 1
|
1
OTUD5 affects DNA break DSB repair
|
1
OTUD5 affects DNA alkylation
|
1
OTUD5 activates DNA alkylation. 1 / 1
|
1
OTUD5 affects Cell Hypoxia
|
1
OTUD5 inhibits Cell Hypoxia. 1 / 1
|
1
reach
"Metabolic tracking revealed that OTUD5 knockdown induced a significantly decreased abundance of tricarboxylic acid (TCA) cycle metabolites (such as M2 citrate, M2 ketoglutarate, M2 succinate, and M2 fumarate), with a compensatory increase in the abundance of glycolytic metabolites (such as M6 G-6-P, M6 F-6-P, M6 F-1, 6-P, M3 pyruvate, and M3 lactate)."
OTUD5 affects 3 L
|
1
reach
"OTUD5 mediates GPX4 deubiquitination to regulate its stability.Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth.Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer.OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD."
MDP-NOD2 axis affects OTUD5
|
1
K63 affects polyubiquitin chains
|
1
K63 affects TRAF3
|
1
K63 affects OTUD5, and polyubiquitin chains
|
1
K48 affects polyubiquitin chains
|
1
Interferon affects OTUD5
|
1
Interferon inhibits OTUD5. 1 / 1
|
1
Inflammatory Bowel Disease affects OTUD5
|
1
OTUD5 binds Inflammatory Bowel Disease. 1 / 1
|
1
HDAC1/2 affects OTUD5
|
1
reach
"To further investigate the role of ERK1/2 and p38 signaling in OTUD5-mediated promotion of HNF4ɑ or HNF1ɑ, we treated the OTUD5-sh HepG2.2.15 cells with ERK1/2-specific pharmacological inhibitor (PD98059), JNK-specific pharmacological inhibitor (SP600125) and p38-specific pharmacological inhibitor (SB203580), and then tested the effect of OTUD5 on the protein level of HNF1α and HNF4α."
E3_Ub_ligase affects OTUD5
|
1
E3_Ub_ligase ubiquitinates OTUD5. 1 / 1
|
1
Deubiquitinase affects OTUD5
|
1
Deubiquitinase decreases the amount of OTUD5. 1 / 1
|
1
CD4+ affects OTUD5
|
1
4-[[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazol-1-yl]-oxomethyl]-2-piperazinone affects OTUD5
|
1
3 L affects YAP1
|
1