IndraLab

Statements


OTUD1 affects TP53
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OTUD1 binds TP53.
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"However, OTUD1 1-311 and OTUD1 1-185 mutants did not interact with p53 ( Fig. 3 D)."

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"We conducted the same coexpression experiment by performing immunoprecipitation with anti-Myc antibody and immunoblotting with anti-Flag antibody and observed a similar interaction between OTUD1 and p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"OTUD1 interacts with p53 and is essential for constant stabilization of p53."

No evidence text available

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"Thus, the results of the present study highlight a new therapeutic opportunity for preventing some disease such as cancer by targeting the OTUD1-p53 axis."

trips
"Moreover, we observed that OTUD1 directly interacted with p53."

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"In addition to these functions, OTUD1 interacts directly with p53 and deubiquitinates p53."

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"Binding assays showed that deletion of the UIM strengthened the interaction between OTUD1 and p53."

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"DNA damage enhances the interaction between OTUD1 and p53, so OTUD1 primarily plays a role in the G2/M and S checkpoints of the cell cycle [36]."

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"DNA damage enhances the interaction between OTUD1 and p53, so OTUD1 primarily plays a role in the G2/M and S checkpoints of the cell cycle [ xref ]."
OTUD1 deubiquitinates TP53.
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OTUD1 deubiquitinates TP53. 8 / 8
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"We also found that OTUD1 directly suppresses p53 ubiquitination in cells through its catalytic activity and that OTUD1 overexpression decreases cell proliferation and increases cell apoptosis."

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"OTUD1, OTUD5 and USP11 directly deubiquitinating p53 and functional proteins were required for p53 stabilization [XREF_BIBR - XREF_BIBR]."

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"In the present study, we found that OTUD1 directly suppressed p53 ubiquitination in cells, leading to its stabilization and activation."

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"Other DUBs, OTUD1 and OTUD5, are also involved in the deubiquitination and stabilization of TP53 in response to DNA damage stress in U2OS cells [51,52]."

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"OTUD1 directly suppresses the ubiquitination of p53 in cells to increase apoptosis and decrease cell proliferation, and a previous study by Piao et al (26) indicated that OTUD1 exerted a pivotal role in regulating p53 stability and activity."

trips
"Our results showed that OTUD1 deubiquitinated p53 and that functional OTUD1 was required for p53 stabilization."

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"OTUD1 acts as a DUB to regulate p53 stability and directly inhibits p53 ubiquitination through its catalytic activity."
OTUD1 activates TP53.
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OTUD1 activates TP53. 4 / 5
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"Therefore, further research is necessary to obtain these answers.This study is the mechanism underlying OTUD1-mediated p53 stability."

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"These results indicate that the C320 residue is essential for maintaining the catalytic activity of OTUD1 and for regulating p53 stability.Next, we examined whether OTUD1 induced p53-dependent cell cy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Moreover, we observed that OTUD1 overexpression induced p53-dependent apoptosis and dramatically inhibited cell growth."

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"Therefore, further studies are necessary to elucidate how the UIM acts OTUD1-mediated p53 deubiquitination.One important finding of the present study is the mechanism underlying OTUD1-mediated p53 reg[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD1 increases the amount of TP53.
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OTUD1 increases the amount of TP53. 2 / 2
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"Transfection of OTUD1 siRNA decreased both OTUD1 and p53 protein levels compared with those in control siRNA-transfected cells ( Fig. 2 D)."

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"Transient OTUD1 overexpression clearly increased p53 level compared with that in control vector-transfected cells ( Fig. 1 B)."
OTUD1 ubiquitinates TP53.
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OTUD1 leads to the ubiquitination of TP53. 1 / 1
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"In contrast, OTUD1 downregulation by using OTUD1 siRNA increased p53 ubiquitination ( Fig. 4 B)."
KEAP1 affects OTUD1
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KEAP1 binds OTUD1.
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7 | 10 16

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"Oikawa et al. (2022) further confirmed KEAP1-OTUD1 interaction and showed that KEAP1 K63 ubiquitination levels were elevated in OTUD1-deficient mouse embryonic fibroblasts, while overexpression of wild-type OTUD1 (but not an ETGE-lacking mutant) reduced KEAP1 ubiquitination in HEK293T cells."

No evidence text available

No evidence text available

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"Mass spectrometric analysis showed that OTUD1 binds KEAP1, and the N-terminal intrinsically disordered region of OTUD1, which contains an ETGE motif, is indispensable for the KEAP1-binding."

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"OTUD1 directly bound with KEAP1, and PGAM5 co-precipitated with OTUD1 only in the presence of KEAP1 (Supplementary Fig. 5d)."

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"Our mass spectrometric analysis reveals that OTUD1 binds KEAP1, a regulator of the transcription factor Nrf2, during ROS-induced oxidative stress [ xref ] ( xref C)."

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"The E3-ligase KEAP1 binds and ubiquitinates OTUD1."

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"The DLG and ETGE motifs in the Neh2 domain of NRF2 are crucial for KEAP1-binding [26], and the C-terminal Kelch domain of KEAP1 binds NRF2 as well as OTUD1."

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"Thus, the biological relevance of the KEAP1-OTUD1 complex remains to be elucidated."
KEAP1 ubiquitinates OTUD1.
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KEAP1 ubiquitinates OTUD1. 3 / 3
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"The E3-ligase KEAP1 binds and ubiquitinates OTUD1."

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"The presence of the KEAP1-substrate ETGE motif indicated that OTUD1 might be ubiquitinated by KEAP1."

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"Deletion of this motif completely disrupted the association of OTUD1 with KEAP1 (Fig. 4e), providing additional evidence for the direct protein-protein binding.The presence of the KEAP1-substrate ETGE motif indicated that OTUD1 might be ubiquitinated by KEAP1."
OTUD1 affects SMURF1
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OTUD1 binds SMURF1.
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"We found that Smurf1 was able to interact with OTUD1 ( xref )."

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"RNA virus infection promotes the interaction between OTUD1 and Smurf1, and binding of Smurf1 to MAVS/TRAF3/TRAF6."

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"Given that RNA viruses activate OTUD1 expression and subsequent Smurf1 upregulation, we further analyze whether OTUD1 interacts with Smurf1, and how Smurf1 is able to affect MAVS/TRAF3/TRAF6 proteins during RNA virus infection."

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"In this study, we reveal that RNA virus infection activates expression of OTUD1, which in turn interacts with Smurf1 and upregulates Smurf1 protein levels by deubiquitination effects."

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"OTUD1 interacts with Smurf1 and functions as a deubiquitinase to remove the K48-linked ubiquitination of Smurf1, prevent its self-ubiquitination degradation, and upregulate its protein level; whereas the binding of Ndfip1 to MAVS recruits Smurf1 to MAVS, and the interaction between Ndfip1 and Smurf1 enhances the self-ubiquitination (possibly k63-linked) and enzyme activity of Smurf1 ( xref ) ( xref , xref )."

No evidence text available

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"We found that SeV infection promoted interaction between OTUD1 and Smurf1 (XREF_FIG)."

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"RNA virus infection promotes the interaction between OTUD1 and Smurf1, and binding of Smurf1 to MAVS/TRAF3/TRAF6."
OTUD1 increases the amount of SMURF1.
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OTUD1 increases the amount of SMURF1. 6 / 6
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"Thus, these data demonstrate that OTUD1 positively regulates cellular levels of Smurf1 by deubiquitination effects."

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"The specific mechanism is: DDIT3 expression induces the production of OTUD1, which promotes the upregulation of Smurf1 expression by deubiquitinating Smurf1, and Smurf1 as E3 will degrade MAVS in a ubiquitin-dependent manner to inhibit IFN-I signaling (194)."

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"During RNA virus infection, OTUD1 is induced through the NF-κB pathway, and OTUD1 deubiquitinates Smurf1 to up-regulate the protein level of Smurf1 in cells."

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"For example, OTUD1 upregulates the protein levels of intracellular Smurf1 by removing the K48-linked polyubiquitin chains of Smurf1, and RNA virus infection promotes the binding of Smurf1 to MAVS, TRAF3, and TRAF6, which leads to ubiquitination-dependent degradation of the three proteins and subsequent potent inhibition of IFNs production (64)."

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"Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination."

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"And OTUD1 upregulates Smurf1 protein levels by removing ubiquitination of Smurf1."
Modified OTUD1 increases the amount of SMURF1. 4 / 4
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"We further found that OTUD1 overexpression upregulated protein level of Smurf1, rather than Smurf2 (XREF_SUPPLEMENTARY)."

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"In this study, we reveal that RNA virus infection activates expression of OTUD1, which in turn interacts with Smurf1 and upregulates Smurf1 protein levels by deubiquitination effects."

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"Overexpression of OTUD1 upregulated exogenous Smurf1 protein levels in a dose dependent manner (XREF_FIG)."

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"RNA virus infection promotes NF-kappaB-dependent expression of OTUD1 that upregulates Smurf1 protein levels."
OTUD1 deubiquitinates SMURF1.
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OTUD1 deubiquitinates SMURF1. 5 / 5
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"During RNA virus infection, OTUD1 is induced through the NF-κB pathway, and OTUD1 deubiquitinates Smurf1 to up-regulate the protein level of Smurf1 in cells."

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"Furthermore, OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1, and Smurf1 degraded MAVS in MDBK cells in a ubiquitination dependent manner, ultimately inhibiting IFN-I production."

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"In addition, RNA viral infection induces OTUD1 expression, which deubiquitinates and stabilizes Smurf1, therefore enhancing Smurf1-mediated MAVS degradation to negatively regulate MAVS function (167)."

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"The specific mechanism is: DDIT3 expression induces the production of OTUD1, which promotes the upregulation of Smurf1 expression by deubiquitinating Smurf1, and Smurf1 as E3 will degrade MAVS in a ubiquitin-dependent manner to inhibit IFN-I signaling (194)."

"Furthermore, <span class="match term0">OTUD1</span> induced upregulation of the E3 ubiquitin ligase <span class="match term1">Smurf1</span> by deubiquitinating <span class="match term1">Smurf1</span>, and <span class="match term1">Smurf1</span> degraded MAVS in MDBK cells in a ubiquitination-dependent manner, ultimately inhibiting IFN-I production"
OTUD1 ubiquitinates SMURF1.
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OTUD1 leads to the ubiquitination of SMURF1. 2 / 2
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"And OTUD1 upregulates Smurf1 protein levels by removing ubiquitination of Smurf1."

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"Furthermore, OTUD1 upregulates protein levels of intracellular Smurf1 by removing Smurf1 ubiquitination."
OTUD1 activates SMURF1.
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OTUD1 activates SMURF1. 2 / 2
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"Next, we analyzed the deubiquitination types of Smurf1 mediated by OTUD1 using two ubiquitin mutants, Ub-R48K (all lysines in Ub are mutated to arginines except lysine 48 residue) and Ub-R63K (all lysines in Ub are mutated to arginines except lysine 63 residue)."

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"RNA virus induced OTUD1 protein regulates Smurf1 ubiquitination and increases the level of Smurf1 protein."
OTUD1 affects CARD9
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OTUD1 binds CARD9.
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"The interaction of OTUD1 and CARD9 was confirmed in HEK‐293T, heart tissues and MPMs isolated from WT mice, respectively (Figure 5D–F)."

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"What's more, ISO stimulation increased OTUD1CARD9 complex formation in heart tissues and MPMs (Figure 5E,F)."

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"OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway."

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"OTUD1 interacts with CARD9 through the OTU + UIM domain and deubiquitinates CARD9 [ xref ] ( xref C)."

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"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33‐linked ubiquitin from CARD9 to promote the assembly of the CARD9‐BCL10‐MALT1 (CBM) complex, without affecting CARD9 stability."

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"These results suggested that the OTUD1CARD9 axis is a new pro‐inflammatory signal in ISO‐challenged macrophages and targeting this axis has a protective effect against ISO‐induced HF."

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"This paper identified the OTUD1CARD9 axis in macrophages as a newly identified modulator of ISO‐stimulated cardiac remodelling."

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"The interaction of OTUD1 and CARD9 was confirmed in HEK‐293T, heart tissues and MPMs isolated from WT mice, respectively (Figure  xref )."

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"What's more, ISO stimulation increased OTUD1CARD9 complex formation in heart tissues and MPMs (Figure  xref )."

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"OTUD1 directly interacts with CARD9 and cleaves polyubiquitin chains off CARD9."
OTUD1 binds CARD9 and K33. 2 / 2
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"32 We demonstrate that OTUD1 binds to the CARD9 and removes the K33‐linked ubiquitin from CARD9, thus promoting the assembly of the CBM complex in macrophages upon ISO stimulation."

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"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability."
OTUD1 deubiquitinates CARD9.
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OTUD1 deubiquitinates CARD9. 5 / 5
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"OTUD1 interacts with CARD9 through the OTU + UIM domain and deubiquitinates CARD9 [44] (Figure 4C)."

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"26 Here, we found that OTUD1 deubiquitinated CARD9 in ISO‐challenged macrophages and mouse hearts."

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"OTUD1 Regulates Antifungal Innate Immunity through Deubiquitination of CARD9."

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"Our previous study showed OTUD1 played an essential role in antifungal innate immunity by deubiquitinating Caspase recruitment domain-containing protein 9 (CARD9) and regulating the CARD9 signaling pathway [18]."

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"Mechanistically, we demonstrated that a deubiquitinating enzyme, ovarian tumour deubiquitinase 1 (OTUD1), directly deubiquitinated CARD9 to promote the assembly of the CBM complex and then activate NF‐κB signalling in macrophages."
OTUD1 deubiquitinates ubiquitinated CARD9. 1 / 1
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"OTUD1 deubiquitinates ubiquitinated CARD9, leading to CARD9 activation."
OTUD1 increases the amount of CARD9.
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OTUD1 increases the amount of CARD9. 1 / 1
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"Overexpressing Flag‐OTUD1 in HEK 293T cells did not increase the protein level of CARD9 (Figure 5K)."
OTUD1 activates CARD9.
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OTUD1 activates CARD9. 1 / 1
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"OTUD1 deficiency down-regulates the CARD9-mediated signaling and dampens production of the proinflammatory elements upon fungal stimulation."
OTUD1 affects STAT3
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OTUD1 binds STAT3.
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"These in vitro studies show that OTUD1 interacts with STAT3 and regulates Tyr-705 phosphorylation and nuclear translocation to module expression of cardiac remodeling genes."

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"These results indicate that STAT3 binds to OTUD1 directly via STAT3 SH2 domain."

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"After identifying STAT3-OTUD1 interaction site, we mutated active sites on OTUD1 (cysteine at position 320 to serine) (Figure xref E)."

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"Mechanistically, we showed that OTUD1 binds to STAT3 and causes deubiquitination of STAT3."

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"This study further elucidated that OTUD1 bound to the SH2 domain of STAT3 through its cysteine site at position 320, thereby exerting the effect of deubiquitination (Ref. xref )."

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"To confirm this potential interaction between OTUD1 and STAT3, we transfected NVRMs and HEK-293T cells with Flag-tagged OTUD1 and showed that STAT3 interacts with OTUD1 following co-IP assay (Figure 5C-D)."

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"We tested the idea that OTUD1 binding to STAT3 may disrupt STAT3-KPNA3 association, which possibly reduces nuclear translocation."

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"Mechanistically, we showed that OTUD1 binds to STAT3 and causes deubiquitination of STAT3."

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"Our detailed mechanistic studies showed that OTUD1 interacts with signal transducer and activator of transcription 3 (STAT3) and leads to deubiquitination and increased phosphorylation of STAT3."

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"OTUD1 interacts directly with STAT3 and promotes STAT3 activation."
OTUD1 deubiquitinates STAT3.
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OTUD1 deubiquitinates STAT3. 7 / 7
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"Mechanistically, OTUD1 bounds to the SH2 domain of STAT3 and causes deubiquitination of STAT3."

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"Finally, OTUD1 overexpression by AAV9 vector increases Ang II-induced cardiac remodeling in mice and OTUD1-regulated responses can be inhibited by blocking STAT3.Conclusion: Cardiomyocyte OTUD1 promotes pathological cardiac remodeling and dysfunction by deubiquitinating STAT3."

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"From this setup, we show that OTUD1 reduces the ubiquitination of STAT3 (Figure 6A)."

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"The authors found that OTUD1 deubiquitinates and stabilizes STAT3, thereby enhancing its activity and contributing to adverse cardiac remodeling and dysfunction 57."

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"For example, OTUD1 affects the inflammatory response by deubiquitinating the STAT3 gene and influences pro-inflammatory cytokine production by cleaving its ubiquitin chain through direct interaction with CARD9 (Chen et al., 2021); OTUD1 also affects IFN signaling and innate immune response by stabilizing TyK2 protein (Zhang et al., 2022)."

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"Although the involved lysine residues in STAT3 are not identified, this is the first time to present a K63-linked deubiquitination of STAT3 by OTUD1 to regulate STAT3 activity."

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"We mapped SH2 domain on STAT3 as the OTUD1 binding site and showed that OTUD1 deubiquitinates STAT3 to increase p-STAT3 levels and STAT3 nuclear translocation."
OTUD1 activates STAT3.
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OTUD1 activates STAT3. 7 / 7
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"These results demonstrate that OTUD1 promotes Ang II-induced cardiac remodeling and dysfunction through activating STAT3."

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"The first study demonstrated that OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes."

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"In addition, OTUD1 and USP15 appear to modulate cardiac myocyte remodeling in the context of heart failure, the former by targeting STAT3 [137,138]."

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"OTUD1 interacts directly with STAT3 and promotes STAT3 activation."

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"Conversely, expression of OTUD1 in cardiomyocytes exacerbated Ang II-induced p-STAT3 (Figure 5F, Figure S5B)."

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"OTUD1 increases Ang II-induced cardiomyocyte myocardial hypertrophy and fibrosis by regulating STAT3."

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"OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes."
OTUD1 decreases the amount of STAT3.
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OTUD1 decreases the amount of STAT3. 1 / 1
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"In this setting, OTUD1 knockdown prevented Ang II-induced p-STAT3 levels in cardiomyocytes (Figure 5E, Figure S5A)."
OTUD1 affects MAP3K5
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OTUD1 binds MAP3K5.
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"Then, we proceeded to investigate the in vivo function of the Otud1-Ask1 axis."

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"OTUD1 physically interacts with ASK1 and is involved in MAPK pathway regulation, which is essential for the maintenance of CSC properties (Fig.  xref )."

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"We then examined the interaction between OTUD1 and ASK1."

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"Reciprocal coimmunoprecipitation (Co-IP) revealed that OTUD1 binds to ASK1 (Fig.  xref ), and their interaction was not influenced by the enzymatically inactive OTUD1 C320A mutant (Fig.  xref )."

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"As shown in Fig.  xref h, both the N-terminus and C-terminus of OTUD1 bound to ASK1."

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"We then examined the interaction between OTUD1 and ASK1."

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"Reciprocal coimmunoprecipitation (Co-IP) revealed that OTUD1 binds to ASK1 (Fig. 2e), and their interaction was not influenced by the enzymatically inactive OTUD1 C320A mutant (Fig. 2f)."

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"OTUD1 is involved in MAPK/JNK pathway regulation and physically interacts with ASK1."

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"Because OTUD1 strongly bound to ASK1, we sought to determine whether ASK1 could be recruited to OTUD1-based aggresomes."

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"As shown in Fig. 2g, h, both the N-terminus and C-terminus of OTUD1 bound to ASK1."
OTUD1 increases the amount of MAP3K5.
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OTUD1 increases the amount of MAP3K5. 6 / 6
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"As shown in Fig. 2d, ectopic OTUD1 expression upregulated apoptosis signal-regulation kinase-1 (ASK1) and increased ASK1 phosphorylation levels."

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"In addition, loss of OTUD1 reduced the c-Jun phosphorylation level in SKOV3, OVCAR8 and CAOV3 cells (Supplementary Fig. 2e), implying that OTUD1 probably regulates OSCS by activating the JNK/c-Jun pathway.Moreover, depletion of OTUD1 reduced the ASK1 phosphorylation level in SKOV3 and OVCAR8 cells (Supplementary Fig. 2f)."

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"As shown in Fig. 3b, ectopic expression of WT OTUD1 increased the ASK1 level, consistent with the observation that OTUD1 reduced ASK1 K48 ubiquitination."

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"Surprisingly, expression of the OTUD1 deubiquitinase-dead C320A mutant increased the ASK1 protein level to an extent comparable to that resulting from WT OTUD1 expression (Fig. 3b)."

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"As shown in Fig. 4g, after treating SKOV3 cells with doxorubicin (DOX) for 12 h, ectopic expression of OTUD1 but not Δ105–164 (M1) increased the phosphorylation levels of ASK1 at Thr838 and the expression levels of the downstream phosphorylated forms of JNK and c-Jun, all of which indicate ASK1 activation."

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"IHC analysis of xenograft tumors also revealed that OTUD1 but not OTUD1 increased ASK1 protein levels and JNK phosphorylation (Supplementary Fig. 5h)."
OTUD1 phosphorylates MAP3K5.
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OTUD1 leads to the phosphorylation of MAP3K5. 4 / 4
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"As shown in Fig. 2d, ectopic OTUD1 expression upregulated apoptosis signal-regulation kinase-1 (ASK1) and increased ASK1 phosphorylation levels."

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"Despite significant advancements in the identification of potential molecular targets and signaling pathways within the realm of cardiac hypertrophy 34-37, the existing clinical pharmacological strategies for managing this condition remain unsatisfactory.To the best of our knowledge, this is the first study to demonstrate that OTUD1 promotes pathological cardiac hypertrophy by upregulating ASK1 phosphorylation."

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"IHC analysis of xenograft tumors also revealed that OTUD1 but not OTUD1 increased ASK1 protein levels and JNK phosphorylation (Supplementary Fig. 5h)."

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"Mechanically, Otud1 directly interacts with Pgam5 and Ask1 to inhibit Pgam5 ubiquitination degradation and subsequently elevate Ask1 phosphorylation."
OTUD1 activates MAP3K5.
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OTUD1 activates MAP3K5. 4 / 4
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"These results prompted us to investigate whether OTUD1 is sufficient to activate ASK1 downstream signaling and whether its deubiquitinase activity is needed for this regulation."

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"OTUD1 promotes ASK1 stability in a largely deubiquitinase-independent manner."

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"OTUD1 promotes Cardiac Hypertrophy in an ASK1-Dependent Manner."

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"All the above results demonstrated that OTUD1-based aggresomes contribute to ASK1 protein stabilization and persistent ASK1/JNK activation and that this function is mediated by a region (aa 105–164) located in the OTUD1 N-terminal intrinsically disordered region."
OTUD1 dephosphorylates MAP3K5.
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OTUD1 leads to the dephosphorylation of MAP3K5. 2 / 2
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"Mechanically, Otud1 directly interacts with Pgam5 and Ask1 to inhibit Pgam5 ubiquitination degradation and subsequently elevate Ask1 phosphorylation."

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"In addition, loss of OTUD1 reduced the c-Jun phosphorylation level in SKOV3, OVCAR8 and CAOV3 cells (Supplementary Fig. 2e), implying that OTUD1 probably regulates OSCS by activating the JNK/c-Jun pathway.Moreover, depletion of OTUD1 reduced the ASK1 phosphorylation level in SKOV3 and OVCAR8 cells (Supplementary Fig. 2f)."
OTUD1 affects BST2
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OTUD1 binds BST2.
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"In addition, in this study, we only used labeled proteins to verify the interaction between OTUD1 and BST-2, and did not verify endogenous protein interaction or deeply explore the relationship between OTUD1, BST-2 and Vpu."

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"While this mutation did not disrupt the interaction between OTUD1 and BST-2 ( xref D), it abolished the ability of OTUD1 to reduce BST-2 ubiquitination ( xref E,F)."

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"In this study, we conducted a small interfering RNA (siRNA) screening of human DUBs and determined that OTUD1 interacts with BST-2, leading to a reduction in its K48- and K63-linked ubiquitination."

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"While this mutation did not disrupt the interaction between OTUD1 and BST-2 (Figure 4D), it abolished the ability of OTUD1 to reduce BST-2 ubiquitination (Figure 4E,F)."

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"In addition, in this study, we only used labeled proteins to verify the interaction between OTUD1 and BST-2, and did not verify endogenous protein interaction or deeply explore the relationship between OTUD1, BST-2 and Vpu."

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"Notably, OTUD1 interacts with BST-2, reducing its K48- and K63-linked ubiquitination at Lys21, thereby stabilizing its surface expression."

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"Co-immunoprecipitation showed that OTUD1 may interact with BST-2 protein ( xref A,B)."

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"Collectively, these findings indicate that OTUD1 not only interacts with BST-2, but also plays a crucial role in regulating BST-2 protein levels."
OTUD1 increases the amount of BST2.
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OTUD1 increases the amount of BST2. 5 / 5
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"OTUD1 Significantly Enhances BST-2 Surface Expression."

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"Given the substantial increase in BST-2 surface expression induced by OTUD1, their potential interaction was investigated."

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"Collectively, these findings suggest that K21 is a critical site for the regulatory effects of OTUD1 on BST-2 ubiquitination, and that OTUD1 may promote BST-2 expression by specifically catalyzing the removal of K48- and K63-linked ubiquitin chains from K21 of BST-2."

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"OTUD1 Enhances BST-2 Protein Levels Through Direct Interaction."

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"Consistent with the screening results, overexpression of OTUD1 in HeLa cells led to an elevation in the total cellular levels of BST-2 (Figure 2C)."
OTUD1 ubiquitinates BST2.
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OTUD1 leads to the ubiquitination of BST2. 3 / 3
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"We found that OTUD1 overexpression in HEK293T cells led to a significant reduction in BST-2 ubiquitination (Figure 4B), while OTUD1 knockdown resulted in increased ubiquitination levels (Figure 4C)."

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"To explore how OTUD1 modulates polyubiquitination of BST-2, the effects of OTUD1 on specific ubiquitin linkages were examined."

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"Interestingly, the mutation of lysine 21 completely abolished the reduction in BST-2 ubiquitination mediated by OTUD1 in HEK293T cells (Figure 5C), a finding replicated in HEK293T cells (Figure 5D)."
OTUD1 inhibits BST2.
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OTUD1 inhibits BST2. 3 / 3
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"More importantly, OTUD1 increases the inhibitory effect of BST-2 on HIV-1 release, highlighting its potential as a therapeutic target for anti-HIV-1 drug development."

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"These results suggest that up-regulation of OTUD1 inhibits the release of HIV-1 virions by stabilizing BST-2."

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"OTUD1 Potentiates the Inhibitory Effects of BST-2 on HIV-1 Release."
OTUD1 deubiquitinates BST2.
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OTUD1 leads to the deubiquitination of BST2. 2 / 2
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"The results showed that knockdown of OTUD1 significantly increased both K48- and K63-linked ubiquitination of BST-2 (Figure 5A)."

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"Conversely, overexpression of OTUD1 significantly reduced K48- and K63-linked ubiquitination of BST-2 (Figure 5B)."
OTUD1 leads to the deubiquitination of BST2 at position 21. 1 / 1
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"Our results showed that OTUD1 specifically reduced BST-2 ubiquitination at the lysine 21 residue, which is located in its cytosolic domain."
OTUD1 activates BST2.
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OTUD1 activates BST2. 2 / 2
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"OTUD1 Enhances BST-2 Stability."

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"However, when treated with the protein synthesis inhibitor CHX, OTUD1 significantly enhanced the stability of the BST-2 protein (Figure 3C), suggesting that the regulatory effects occur post-translationally."
OTUD1 affects AKT
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OTUD1 binds AKT.
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"We identified a peptide (OUN-36) derived from the OTUD1 N-terminus that binds to the Akt PH domain and disrupts its interaction with PIP3."

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"An in vitro pulldown assay with purified GST-OTUD1 and His-PH demonstrated that the Akt PH domain directly bound to OTUD1 ( Figures 3 D and S3 C)."

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"16 To confirm the identified protein interaction, we expressed both Akt and OTUD1 in HEK293T cells, and coimmunoprecipitation (Co-IP) clearly showed that OTUD1 bound to Akt ( Figure 1 B)."

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"As shown in Figure 1 D, purified OTUD1 bound to Akt."

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"33 Interestingly, our results indicated that OTUD1 binds to the Akt PH domain in a growth factor-independent manner."

sparser
"Notably, the OTUD1 N-terminal intrinsically disordered region contains an abundance of proline (16.9%) and glycine (9.6%) residues, implying that this region is highly flexible, which may facilitate t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Very recently, Fan et al. showed that OTUD1 binds AKT most strongly among 11 OTU family DUBs, and then suppresses its phosphorylation [24]."

sparser
"9 We detected an interaction between OTUD1 and Akt in cells stimulated with EGF or insulin, which activated Akt signaling, and we found that the OTUD1-Akt interaction was not affected ( Figure S1 D)."

sparser
"A 36-amino acid (aa) peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region is responsible for the interaction of OTUD1 with Akt."

sparser
"Consistent with the above results, in the absence of this 36-aa peptide, the interaction between OTUD1 and Akt became nearly undetectable ( Figure 2 G)."
OTUD1 inhibits AKT.
| 4
OTUD1 inhibits AKT. 4 / 4
| 4

reach
"Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells."

reach
"The deubiquitinase OTUD1 noncanonically suppresses Akt activation through its N-terminal intrinsically disordered region."

reach
"The OTUD1 C-terminal deubiquitinase domain decreased Akt K63-linked polyubiquitination, thereby coordinating the inhibitory effect of the N-terminus."

reach
"OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs."
OTUD1 activates AKT.
| 1 2
OTUD1 activates AKT. 3 / 3
| 1 2

eidos
"We therefore show a mechanism by which OTUD1 modulates Akt activity and suggest a potential peptide-based cancer therapeutic strategy implemented by targeting the Akt PH domain ."

reach
"We therefore show a mechanism by which OTUD1 modulates Akt activity and suggest a potential peptide-based cancer therapeutic strategy implemented by targeting the Akt PH domain."

reach
"Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells."
OTUD1 affects SMAD7
5 1 | 14 2
OTUD1 deubiquitinates SMAD7.
1 | 7
OTUD1 deubiquitinates SMAD7. 8 / 8
1 | 7

"Breast cancer metastasis suppressor <span class="match term0">OTUD1</span> deubiquitinates <span class="match term1">SMAD7</span>"

reach
"Further investigation reveals that OTUD1 directly deubiquitinates the TGF-beta pathway inhibitor SMAD7 and prevents its degradation."

reach
"To demonstrate that OTUD1 can directly deubiquitinate SMAD7, we performed in vitro deubiquitination assays."

reach
"This confirms that OTUD1 deubiquitinates SMAD7 in vitro."

reach
"OTUD1 deubiquitinates SMAD7 and sustains SMAD7 stability."

reach
"OTUD1 can deubiquitinate SMAD7 to enable SMURF2 binding and subsequent TβRI turnover on the cell surface to increase breast cancer metastasis ."

reach
"OTUD1 deubiquitinates the TGF-β inhibitor SMAD7 and inhibits p53, thereby increasing the cleavage of caspase-3 and PARP-dependent apoptosis and enhancing tumor suppression248 249.Context-dependent DUBs, such as OTUD3 and USP10, constitute the third type of DUBs that exhibit contradictory functions in various tumors."

reach
"In breast cancer cells, OTUD1 deubiquitinates TGF-β1 inhibitor SMAD7 and increases TGFB receptor 1 turnover 46."
OTUD1 binds SMAD7.
5 | 2
5 | 2

sparser
"Moreover, Zhang et al. reported that OTUD1 binds with and stabilizes SMAD7 to repress the metastasis of breast cancer xref ."

sparser
"OTUD1 associates with SMAD7 and deubiquitinates SMAD7 in vitro."

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OTUD1 activates SMAD7.
| 4
OTUD1 activates SMAD7. 4 / 4
| 4

reach
"The deubiquitinase OTUD1 was found to enable the antagonistic role of SMAD7 on TGF-beta signaling."

reach
"Given our results that OTUD1 enables SMAD7 and SMURF2 function, we examined whether OTUD1 misexpression can regulate TbetaRI levels at the cell surface, the location where intracellular signaling is initiated."

reach
"By doing so, OTUD1 enables SMAD7 function thereby antagonizing TGF-beta and SMAD signaling."

reach
"Ectopic expression of OTUD1-wt, but not OTUD1-CA, prolonged the half-life of endogenous SMAD7."
OTUD1 ubiquitinates SMAD7.
| 2
OTUD1 ubiquitinates SMAD7. 2 / 2
| 2

reach
"OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7."

reach
"20 Zhang et al. revealed that OTUD1 inhibited breast cancer progression by deubiquitinating SMAD7 and then repressed TGF‐β‐induced tumorigenesis."
OTUD1 inhibits SMAD7.
| 1
OTUD1 inhibits SMAD7. 1 / 1
| 1

reach
"Relatively, OTUD1 also can inhibit tumor metastasis by preventing the degradation of SMAD family member 7 (SMDA7), which can inhibit tumor metastasis by blocking TGF-β signaling pathway (Zhang et al., 2017)."
TP53 affects OTUD1
2 | 1 5 12
2 | 1 5 12

sparser
"However, OTUD1 1-311 and OTUD1 1-185 mutants did not interact with p53 ( Fig. 3 D)."

sparser
"We conducted the same coexpression experiment by performing immunoprecipitation with anti-Myc antibody and immunoblotting with anti-Flag antibody and observed a similar interaction between OTUD1 and p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"OTUD1 interacts with p53 and is essential for constant stabilization of p53."

No evidence text available

sparser
"Thus, the results of the present study highlight a new therapeutic opportunity for preventing some disease such as cancer by targeting the OTUD1-p53 axis."

trips
"Moreover, we observed that OTUD1 directly interacted with p53."

sparser
"In addition to these functions, OTUD1 interacts directly with p53 and deubiquitinates p53."

sparser
"Binding assays showed that deletion of the UIM strengthened the interaction between OTUD1 and p53."

reach
"DNA damage enhances the interaction between OTUD1 and p53, so OTUD1 primarily plays a role in the G2/M and S checkpoints of the cell cycle [36]."

sparser
"DNA damage enhances the interaction between OTUD1 and p53, so OTUD1 primarily plays a role in the G2/M and S checkpoints of the cell cycle [ xref ]."
CARD9 affects OTUD1
3 | 6 12
3 | 4 12

reach
"The interaction of OTUD1 and CARD9 was confirmed in HEK‐293T, heart tissues and MPMs isolated from WT mice, respectively (Figure 5D–F)."

reach
"What's more, ISO stimulation increased OTUD1CARD9 complex formation in heart tissues and MPMs (Figure 5E,F)."

sparser
"OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway."

sparser
"OTUD1 interacts with CARD9 through the OTU + UIM domain and deubiquitinates CARD9 [ xref ] ( xref C)."

sparser
"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33‐linked ubiquitin from CARD9 to promote the assembly of the CARD9‐BCL10‐MALT1 (CBM) complex, without affecting CARD9 stability."

sparser
"These results suggested that the OTUD1CARD9 axis is a new pro‐inflammatory signal in ISO‐challenged macrophages and targeting this axis has a protective effect against ISO‐induced HF."

sparser
"This paper identified the OTUD1CARD9 axis in macrophages as a newly identified modulator of ISO‐stimulated cardiac remodelling."

sparser
"The interaction of OTUD1 and CARD9 was confirmed in HEK‐293T, heart tissues and MPMs isolated from WT mice, respectively (Figure  xref )."

sparser
"What's more, ISO stimulation increased OTUD1CARD9 complex formation in heart tissues and MPMs (Figure  xref )."

sparser
"OTUD1 directly interacts with CARD9 and cleaves polyubiquitin chains off CARD9."
OTUD1 binds CARD9 and K33. 2 / 2
| 2

reach
"32 We demonstrate that OTUD1 binds to the CARD9 and removes the K33‐linked ubiquitin from CARD9, thus promoting the assembly of the CBM complex in macrophages upon ISO stimulation."

reach
"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability."
OTUD1 affects NFE2L2
| 12 7
OTUD1 activates NFE2L2.
| 7 5
| 7 5

sparser
"Taken together, these above observations indicate that OTUD1 stabilizes and activates NRF2 through its C320 catalytic residue and ETGE motif."

reach
"These collective findings promoted us to investigate the regulatory mechanism by which deubiquitinase OTUD1 activates NRF2 in the pathogenesis of hepatic I/R injury.Here, we have demonstrated that OTUD1 functions as a specific DUB for NRF2, leading to the stabilization and activation of the NRF2/ARE pathway, thereby results in the reduction of oxidative stress, apoptosis and inflammation in I/R-challenged liver."

reach
"Considering that OTUD1 possess DUB activity [28] and NRF2 activation is tightly regulated by deubiquitination [22], it is postulated that OTUD1 may activate NRF2 by removing ubiquitin chains from NRF2."

sparser
"These collective findings promoted us to investigate the regulatory mechanism by which deubiquitinase OTUD1 activates NRF2 in the pathogenesis of hepatic I/R injury."

reach
"Keeping in line with the data, luciferase assay revealed that overexpression of OTUD1-WT markedly enhanced NRF2 luciferase activity."

reach
"Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury."

sparser
"Considering that OTUD1 possess DUB activity [ xref ] and NRF2 activation is tightly regulated by deubiquitination [ xref ], it is postulated that OTUD1 may activate NRF2 by removing ubiquitin chains from NRF2."

sparser
"Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury."

reach
"In short, OTUD1 prefers abolishing proteosome-mediated NRF2 degradation rather than modulating NRF2 function through removing K63 polyubiquitin scaffold.Due to its robust cytoprotective role in preventing oxidative stress and inflammation, NRF2 activation is considered a promising therapeutic strategy for numerous diseases characterized by oxidative stress [40]."

reach
"We utilized cycloheximide (CHX) to inhibit protein translation and observed that OTUD1 overexpression dramatically prolonged the half-life of NRF2 protein in AML12 cells (Fig. 4C), signifying its role in stabilizing NRF2."
OTUD1 binds NFE2L2.
| 2 2
| 2 2

sparser
"Our findings demonstrated that the interaction between OTUD1 and NRF2 primarily occurred through its Neh2 domain (aa 1–111), as the Neh2 deletion truncation (NRF2-E) failed to bind with OTUD1 in HEK293T cells ( xref D)."

sparser
"Collectively, these results suggest a physical interaction between OTUD1 and NRF2."

reach
"Our findings demonstrated that the interaction between OTUD1 and NRF2 primarily occurred through its Neh2 domain (aa 1–111), as the Neh2 deletion truncation (NRF2-E) failed to bind with OTUD1 in HEK293T cells (Fig. 5D)."

reach
"Our mass spectrometric analysis reveals that OTUD1 binds KEAP1, a regulator of the transcription factor Nrf2, during ROS-induced oxidative stress [19] (Figure 5C)."
OTUD1 increases the amount of NFE2L2.
| 3
OTUD1 increases the amount of NFE2L2. 3 / 3
| 3

reach
"The slowed degradation of Nrf2 and YAP with the high expression of USP17 and OTUD1 was detected in the chemoresistant PDAC cell line, and the knockdown of OTUD1 reduced the levels of Nrf2 and YAP, and cell growth."

reach
"As expected, OTUD1 dose-dependently increased the protein level of NRF2 (Fig. 4B)."

reach
"Our results showed that overexpression of OTUD1-WT strongly increased NRF2 protein levels, while overexpression of either the inactive mutant C320S (M1) or ETGE deletion mutant (M2) only slightly increased NRF2 protein levels."
OTUD1 affects PRDX4
4 | 9 5
OTUD1 binds PRDX4.
4 | 2 5
4 | 2 5

sparser
"To map and localize the OTUD1-PRDX4 interaction, we used the full length (FL) and the Δ1-38 PRDX4 constructs."

sparser
"However, a precise mechanism how OTUD1-PRDX4 axis mediates the Ig synthesis remained unclear."

No evidence text available

sparser
"In summary, our work unveils the OTUD1-PRDX4 axis as a yet undescribed regulatory pathway driving Ig production and PI sensitivity in MM cells and highlights importance of OTUD1 in myeloma proliferation (Fig.  xref )."

reach
"At the same time, OTUD1 binds and elevates PRDX4 protein amount."

reach
"Co-immunoprecipitation of OTUD1 and PRDX4 complexes was performed by lysing RPMI8226 cells in immunoprecipitation buffer (20 mM TRIS, pH 7.5, 150 mM NaCl, 0.5% NP40) containing phosphatase and protease inhibitor cocktail (Thermo Fisher Scientific), 20 mM N-ethylmaleimide, and 5 mM iodacetamide for 1 h on ice."

No evidence text available

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sparser
"Initially, we validated the OTUD1-PRDX4 interaction in series of reciprocal co-immunoprecipitations with both tagged and endogenous proteins (Fig.  xref )."
OTUD1 increases the amount of PRDX4.
| 3
OTUD1 increases the amount of PRDX4. 3 / 3
| 3

reach
"Elucidation of how OTUD1 and PRDX4 are linked to protein synthesis will require further research.Interestingly, OTUD1 binds and selectively promotes PRDX4 levels leaving other components of the ER folding machinery intact."

reach
"Moreover, OTUD1 oe led to a higher amount of FL PRDX4 but not Δ1-38 PRDX4 in the ER fractions (Supplementary Fig. 5c, d), further suggesting that OTUD1 protects PRDX4 from ERAD.A previous study described OTUD2 (YOD1), a close homolog of OTUD1, as a non-selective regulator of protein retrotranslocation from ER."

reach
"Together these results support the model where OTUD1 increases PRDX4 protein amount which promote the formation of new IgL molecules by enforcing translation elongation."
OTUD1 deubiquitinates PRDX4.
| 3
OTUD1 deubiquitinates PRDX4. 3 / 3
| 3

reach
"We found OTUD1 selectively deubiquitinates PRDX4 during retranslocation from ER, thus protecting it from ERAD.PRDX4 is a critical component of the ER folding machinery where it mediates the formation of intra- and intermolecular disulfide bonds during oxidative protein folding ."

reach
"Mechanistically, OTUD1 deubiquitinates peroxiredoxin 4 (PRDX4), protecting it from endoplasmic reticulum (ER)-associated degradation."

reach
"Thus, we conclude that OTUD1 deubiquitinates PRDX4 and regulates its abundance, possibly by protecting it from degradation.To date, no activity of ubiquitin ligases was detected inside ER ."
OTUD1 decreases the amount of PRDX4.
| 1
OTUD1 decreases the amount of PRDX4. 1 / 1
| 1

reach
"Additionally, OTUD1 oe increased while OTUD1 knock-down decreased the amount of endogenous PRDX4 protein (Fig. 5i, j) without any effect on the levels of PRDX4 mRNA (Supplementary Fig. 5e)."
OTUD1 affects PGAM5
1 | 11 5
OTUD1 binds PGAM5.
1 | 4 5
1 | 3 5

sparser
"The binding of Pgam5 and Otud1 was validated by both exogenous and endogenous immunoprecipitation."

reach
"The binding of Pgam5 and Otud1 was validated by both exogenous and endogenous immunoprecipitation."

reach
"This upregulated OTUD1 then interacts with and deubiquitinates PGAM5, promoting ASK1 phosphorylation and the activation of the p38/JNK MAPK signaling pathway."

No evidence text available

sparser
"Therefore, our findings showed that OTUD1 interacts with PGAM5 and promotes its ubiquitination and degradation."

reach
"OTUD1 binds to and deubiquitinates PGAM5."

sparser
"OTUD1 binds to and deubiquitinates PGAM5."

sparser
"Conclusion : Our findings confirm that targeting the OTUD1-PGAM5 axis holds significant potential as a therapeutic approach for heart failure associated with pathological hypertrophy."

sparser
"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure xref C-D)."
OTUD1 binds PGAM5 and 293T. 1 / 1
| 1

reach
"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure 6C-D)."
OTUD1 deubiquitinates PGAM5.
| 5
OTUD1 deubiquitinates PGAM5. 5 / 5
| 5

reach
"METTL3-mediated m6A modification of OTUD1 aggravates press overload induced myocardial hypertrophy by deubiquitinating PGAM5."

reach
"Mechanistically, OTUD1 facilitated the procession of cardiac hypertrophy by directly binding to and deubiquitinating PGAM5 in a manner dependent on K63 ubiquitin chains, leading to enhanced ASK1 phosphorylation and p38/JNK MAPK signal pathway activation in cardiomyocytes."

reach
"OTUD1 binds to and deubiquitinates PGAM5."

reach
"Our findings indicated that the deletion of the OTU domain did not exhibit any pro-hypertrophic effects on the NRVMs (Figure S7), suggesting the critical role of OTU domain in OTUD1-induced cardiac hypertrophy.Given that DUBs play a role in the modulation of biological activities by influencing the degradation or function of substrate proteins, our subsequent investigation aimed to determine whether Otud1 could deubiquitinating pgam5."

reach
"This upregulated OTUD1 then interacts with and deubiquitinates PGAM5, promoting ASK1 phosphorylation and the activation of the p38/JNK MAPK signaling pathway."
OTUD1 ubiquitinates PGAM5.
| 1
OTUD1 leads to the ubiquitination of PGAM5. 1 / 1
| 1

reach
"Mechanically, Otud1 directly interacts with Pgam5 and Ask1 to inhibit Pgam5 ubiquitination degradation and subsequently elevate Ask1 phosphorylation."
OTUD1 increases the amount of PGAM5.
| 1
OTUD1 increases the amount of PGAM5. 1 / 1
| 1

reach
"We demonstrated that Otud1 promoted cardiac hypertrophy by stabilizing Pgam5 protein expression, leading to elevated Ask1 phosphorylation."
OTUD1 affects IRF3
5 1 | 6 5
OTUD1 binds IRF3.
5 | 1 5
5 | 5

sparser
"Subsequent co-immunoprecipitation assay verified the association of OTUD1 with IRF3 ( Fig. 3 B)."

sparser
"In addition to T407P and G430V which are assumed to neutral mutations, other OTUD1 mutants impair its suppressive effects on innate immunity through blocking the association of OTUD1 with IRF3 or dire[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

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sparser
"In addition to its role in T cell activation and function, FOXO3 elicits an inhibitory effect on the innate immune response through activation of OTUD1-IRF3 signaling."

No evidence text available

sparser
"OTUD1 interacts with IRF3 to remove the K63-linked poly-ubiquitin chains on IRF3 and to suppress the interferon activity."

sparser
"We next used immunofluorescence assays to confirm the association of OTUD1 with IRF3."

No evidence text available
OTUD1 binds IRF3 and K63. 1 / 1
| 1

reach
"As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63 linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity."
OTUD1 inhibits IRF3.
| 4
OTUD1 inhibits IRF3. 4 / 4
| 4

reach
"OTUD1 can inhibit the transcriptome activity of IRF3, thus maintaining immune homeostasis in cells and hence dose OTUD3, PTUD4, and A20 (16, 24–26)."

reach
"In both RNA and DNA virus infections, OTUD1 inhibits IRF3-dependent type I IFN production [ 22 ]."

reach
"In VSV-infected cells, OTUD1 prevented the binding of IRF3 to the promotor region of type IFN I genes by cleaving K6-linked ubiquitin chains from IRF3."

reach
"OTUD1 reportedly restricts IRF3 by removing its critical K6-linked ubiquitin chain from K105 (Figure 4A)."
OTUD1 ubiquitinates IRF3.
| 1
OTUD1 ubiquitinates IRF3. 1 / 1
| 1

reach
"Among these, MID1, TRIM21, C-CBL, TRIM26, OTUD1, RBCK1, PLPRO, POH1, and RNF5 have been reported to be involved in the ubiquitination of IRF3 (11 – 19)."
OTUD1 deubiquitinates IRF3.
1 |
OTUD1 deubiquitinates IRF3. 1 / 1
1 |

"As a deubiquitinase, <span class="match term0">OTUD1</span> directly interacts with transcription factor <span class="match term1">IRF3</span> and removes the K63-linked poly-ubiquitin chains on <span class="match term1">IRF3</span> Lysine 98, which inhibits <span class="match term1">IRF3</span> nuclear translocation and transcriptional activity"
| 1 14
| 1 8

reach
"OTUD1 can activate caspase-dependent apoptosis, with interaction between C-Caspase-3 and C-Caspase-9 [ 37 ]; however, this phenomenon has only been proven in esophageal carcinoma and renal carcinoma [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We also found that OTUD1 directly suppresses p53 ubiquitination in cells through its catalytic activity and that OTUD1 overexpression decreases cell proliferation and increases cell apoptosis."

reach
"The results showed that Otud1 overexpression led to a reduction in serum ALT and AST levels (Fig. 3A), as well as a decrease in liver tissue necrosis and apoptosis induced by hepatic I/R compared to control mice (Fig. 3B and C)."

eidos
"OTUD1 knockdown inhibited melatonin-induced Bim upregulation and apoptosis in cancer cells ."

reach
"Moreover, we observed that OTUD1 overexpression induced p53-dependent apoptosis and dramatically inhibited cell growth."

reach
"OTUD1 overexpression reduces cell proliferation and increases apoptosis [35]."

reach
"Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation."

reach
"Moreover, OTUD1 overexpression promoted the cleavage of caspase-3 and PARP, which are apoptotic indicators, and increased apoptosis."
Mutated OTUD1 activates apoptotic process. 1 / 1
| 1

reach
"We also tested the effect of OTUD1 mutants on H/R induced changes of apoptosis, MMP and ROS in AML12 cells."
| 6

reach
"OTUD1 also suppresses TNF-α-induced apoptosis and necroptosis."

reach
"In this study, we showed that the genetic deficiency of OTUD1 accelerated the TNF-α-induced apoptosis and necroptosis, and the basal K63 ubiquitination of RIP3 was enhanced in Otud1 -MEFs (Figs."

reach
"OTUD1 negatively regulates the canonical NF-kappaB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway."

reach
"OTUD1 suppresses TNF-alpha-induced apoptosis and necroptosis."

reach
"OTUD1 Inhibits Apoptosis of Fibroblast."

reach
"Cell samples were stained and incubated with Annexin V and PI, the apoptosis rate of the si-OTUD1 group was significantly higher than that of the NC group (P < 0.05, Figure 7B) according to the results of the flow cytometry assay (Figure 7A), demonstrating that OTUD1 gene can significantly inhibit fibroblast apoptosis."
OTUD1 affects Interferon
| 2 14
OTUD1 inhibits Interferon.
| 2 8
| 2 8

eidos
"] OTUD1 was also reported to inhibit IFN production during RNA virus infection ."

reach
"After the BVDV infection, the expression of OTUD1 is upregulated in DDIT3-overexpressing cells and inhibits IFN antiviral responses."

reach
"OTUD1 Negatively Regulates Type I IFN Induction by Disrupting Noncanonical Ubiquitination of IRF3."

reach
"Therefore, the authors concluded that the DDIT3–OTUD1–MAVS pathway suppresses IFN production through the degradation of MAVS.Patients with major depressive disorder (MDD) have a higher risk of viral infection."

eidos
"Hence , OTUD1 cleaves the K6-linked ubiquitin chain and leads to the disassociation of IRF3 from the promoter region of target genes , thereby attenuating type I IFN induction ."

reach
"Furthermore, OTUD1 inhibits type 1 IFN induction after virus infection through cleaving noncanonical K6-linked ubiquitination of IRF3 [83]."

reach
"OTUD1 then removes the K63-linked ubiquitin chain from K98 of IRF3 and attenuates the RIG-I-like receptors (RLRs)-mediated IFN production pathway (Figure 4A)."

reach
"Additionally, OTUD1 downregulates the induction of type I IFN by cleaving the viral infection-induced atypical K6-linked ubiquitination of IRF3 [31]."

reach
"Taken together, these results suggest that both Smurf1 and the deubiquitinase activity of OTUD1 are required for the downregulation of MAVS/TRAF3/TRAF6 signalosome proteins, which results in the OTUD1 mediated inhibition of interferon antiviral response."

reach
"The aforementioned results prove that Smurf1 is important for OTUD1 mediated inhibition of interferon antiviral response."
OTUD1 activates Interferon.
| 6
| 6

reach
"Ovarian tumor deubiquitinase 1 (OTUD1) is a critical member of OUT deubiquitinases, which has been identified as a negative regulator in IRF3-mediated interferon signaling in mammals."

reach
"OTUD1 could upregulate the interferon (IFN) antiviral pathway and improve the immune ability (Zhang et al., 2020)."

reach
"Importantly, otud1 -deficient mice were more resistant against lethal RNA (VSV) and DNA (HSV) virus infection and produced more protective type I IFN and cytokines [ 22 ]."

reach
"OTUD1 negatively regulates the canonical NF-kappaB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway."

reach
"Both Smurf1 and the deubiquitinase activity of OTUD1 are required for OTUD1 mediated downregulation of MAVS/TRAF3/TRAF6 and inhibition of interferon antiviral response."

reach
"OTUD1 activates IFN antiviral signaling."
OTUD1 affects AIFM1
8 | 2 6
OTUD1 binds AIFM1.
8 | 1 6
8 | 1 6

sparser
"We next performed in vitro pulldown assays to investigate whether OTUD1 could directly bind to AIF."

sparser
"As described above, OTUD1 binds and regulates the mitochondrial antiapoptotic protein AIF, and this interaction is associated with caspase-dependent apoptosis and caspase-independent parthanatos with OXPHOS-related ROS production ( xref C) [ xref ]."

sparser
"Co‐IP assays showed that AIF selectively binds to the linker domain of OTUD1 (Figure S3C, Supporting Information), while OTUD1 associates with the NADH binding and Loop domains of AIF (Figure S3D, Supporting Information)."

No evidence text available

No evidence text available

No evidence text available

reach
"As described above, OTUD1 binds and regulates the mitochondrial antiapoptotic protein AIF, and this interaction is associated with caspase-dependent apoptosis and caspase-independent parthanatos with OXPHOS-related ROS production (Figure 3C) [36]."

No evidence text available

No evidence text available

No evidence text available
OTUD1 deubiquitinates AIFM1.
| 1
OTUD1 deubiquitinates AIFM1 on K244. 1 / 1
| 1

reach
"As an example of AIF posttranslational modifications, it was reported that the X-linked inhibitor of apoptosis (XIAP) ubiquitinates AIF at K255 and consequently regulates AIF pro-apoptotic features, rather than its proteasomal degradation or NADH oxidoreductase properties.78 79 On the other hand, OTU deubiquitinase 1 (OTUD1) directly deubiquitinates AIF at K244 and alters AIF binding to CHCHD4, resulting in impaired OXPHOS and swollen mitochondria lacking intact cristae."
AKT affects OTUD1
| 1 15
| 1 15

sparser
"We identified a peptide (OUN-36) derived from the OTUD1 N-terminus that binds to the Akt PH domain and disrupts its interaction with PIP3."

sparser
"An in vitro pulldown assay with purified GST-OTUD1 and His-PH demonstrated that the Akt PH domain directly bound to OTUD1 ( Figures 3 D and S3 C)."

sparser
"16 To confirm the identified protein interaction, we expressed both Akt and OTUD1 in HEK293T cells, and coimmunoprecipitation (Co-IP) clearly showed that OTUD1 bound to Akt ( Figure 1 B)."

sparser
"As shown in Figure 1 D, purified OTUD1 bound to Akt."

sparser
"33 Interestingly, our results indicated that OTUD1 binds to the Akt PH domain in a growth factor-independent manner."

sparser
"Notably, the OTUD1 N-terminal intrinsically disordered region contains an abundance of proline (16.9%) and glycine (9.6%) residues, implying that this region is highly flexible, which may facilitate t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Very recently, Fan et al. showed that OTUD1 binds AKT most strongly among 11 OTU family DUBs, and then suppresses its phosphorylation [24]."

sparser
"9 We detected an interaction between OTUD1 and Akt in cells stimulated with EGF or insulin, which activated Akt signaling, and we found that the OTUD1-Akt interaction was not affected ( Figure S1 D)."

sparser
"A 36-amino acid (aa) peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region is responsible for the interaction of OTUD1 with Akt."

sparser
"Consistent with the above results, in the absence of this 36-aa peptide, the interaction between OTUD1 and Akt became nearly undetectable ( Figure 2 G)."
OTUD1 affects MAVS
| 13 2
OTUD1 decreases the amount of MAVS.
| 5
OTUD1 decreases the amount of MAVS. 5 / 5
| 5

reach
"In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6."

reach
"OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."

reach
"In this process, OTUD1 negatively regulates the protein levels of mitochondrial antiviral-signaling protein (MAVS) and the TNF receptor-associated factor 3 (TRAF3) and TRAF6 E3s."

reach
"OTUD1 negatively regulates MAVS protein levels by the upregulation of Smurf1 (Figure 4A)."

reach
"Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."
OTUD1 inhibits MAVS.
| 3
OTUD1 inhibits MAVS. 3 / 3
| 3

reach
"These data indicate that OTUD1 inhibits the IFNs antiviral response downstream of MAVS and upstream of TBK1."

reach
"In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited."

reach
"In addition, RNA viral infection induces OTUD1 expression, which deubiquitinates and stabilizes Smurf1, therefore enhancing Smurf1-mediated MAVS degradation to negatively regulate MAVS function (167)."
OTUD1 binds MAVS.
| 1 2
| 1 1

sparser
"Our data showed that OTUD1 was able to interact with MAVS ( xref )."

reach
"To further identify the signaling proteins targeted by OTUD1, the interaction between OTUD1 and MAVS was first analyzed."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
OTUD1 activates MAVS.
| 3
OTUD1 activates MAVS. 3 / 3
| 3

reach
"Therefore, we tried to analyze whether Smurf1 could be required for OTUD1 mediated downregulation of MAVS."

reach
"Our data showed that knockdown of Smurf1 significantly inhibited OTUD1 mediated MAVS downregulation (XREF_FIG)."

reach
"Among them, OTUD4 is induced in an IRF3/7-dependent manner, and OTUD1 increases the stability of MAVS during viral infection by directly removing the K48-linked ubiquitination of MAVS, thereby promoting RLR-mediated innate immune signals (132)."
OTUD1 deubiquitinates MAVS.
| 1
OTUD1 leads to the deubiquitination of MAVS. 1 / 1
| 1

reach
"Furthermore, OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1, and Smurf1 degraded MAVS in MDBK cells in a ubiquitination dependent manner, ultimately inhibiting IFN-I production."
AIFM1 affects OTUD1
8 | 1 6
8 | 1 6

sparser
"We next performed in vitro pulldown assays to investigate whether OTUD1 could directly bind to AIF."

sparser
"As described above, OTUD1 binds and regulates the mitochondrial antiapoptotic protein AIF, and this interaction is associated with caspase-dependent apoptosis and caspase-independent parthanatos with OXPHOS-related ROS production ( xref C) [ xref ]."

sparser
"Co‐IP assays showed that AIF selectively binds to the linker domain of OTUD1 (Figure S3C, Supporting Information), while OTUD1 associates with the NADH binding and Loop domains of AIF (Figure S3D, Supporting Information)."

No evidence text available

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reach
"As described above, OTUD1 binds and regulates the mitochondrial antiapoptotic protein AIF, and this interaction is associated with caspase-dependent apoptosis and caspase-independent parthanatos with OXPHOS-related ROS production (Figure 3C) [36]."

No evidence text available

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reach
"OTUD1 overexpression inhibits NSCLC cell proliferation, migration and invasion."

reach
"Our results indicated that upregulation of OTUD1 expression inhibits TNBC cell proliferation and enhances its sensitivity to doxorubicin."

reach
"We also found that OTUD1 directly suppresses p53 ubiquitination in cells through its catalytic activity and that OTUD1 overexpression decreases cell proliferation and increases cell apoptosis."

reach
"Taken together, these results suggested that overexpression OTUD1 notably inhibits NSCLC cell progression including proliferation, migration and invasion."

reach
"These results suggest that OTUD1 inhibits cell proliferation by regulating cell cycle and apoptosis.p53 is a master transcription factor that performs critical regulatory functions in cells."

reach
"OTUD1 knockdown promotes NSCLC cell proliferation, migration and invasion."

reach
"OTUD1 overexpression reduces cell proliferation and increases apoptosis [35]."

reach
"OTUD1 negatively regulates the cell cycle to inhibit the abnormal proliferation of cancer cells, since OTUD1 interacts with phosphatase and tensin homolog (PTEN), a negative regulator of the AKT (also known as protein kinase B) and NF-κB signaling pathways, and regulates its stability (Figure 2C)."

reach
"Depletion of endogenous OTUD1 potentiated the capacity of RAS transformed MCF10A cells to form tumor organoids in 3D Matrigel but did not inhibit tumor cell survival and proliferation under standard 2D culture conditions."

reach
"OTUD1 inhibited proliferation and migration of lung cancer cells in vitro."

reach
"As expected, OTUD1 oe suppressed myeloma cell growth while introduction of sh OTUD1 promoted proliferation (Fig. 2f, g)."

reach
"Our findings demonstrated that novel-miR-741 inhibited the proliferation, and migration of crop fibroblasts, while OTUD1 promoted the proliferation and migration of crop fibroblasts."

reach
"OTUD1 Promotes Proliferation and Migration of Fibroblast."

reach
"On the other hand, differences in myeloma cell proliferation caused by differential OTUD1 expression were not changed by normalizing PRDX4 protein levels or by restoring the IgL levels (Supplementary Fig. 6a–c)."
SMURF1 affects OTUD1
3 | 4 6
SMURF1 binds OTUD1.
3 | 3 6
3 | 3 6

sparser
"We found that Smurf1 was able to interact with OTUD1 ( xref )."

reach
"RNA virus infection promotes the interaction between OTUD1 and Smurf1, and binding of Smurf1 to MAVS/TRAF3/TRAF6."

reach
"Given that RNA viruses activate OTUD1 expression and subsequent Smurf1 upregulation, we further analyze whether OTUD1 interacts with Smurf1, and how Smurf1 is able to affect MAVS/TRAF3/TRAF6 proteins during RNA virus infection."

sparser
"In this study, we reveal that RNA virus infection activates expression of OTUD1, which in turn interacts with Smurf1 and upregulates Smurf1 protein levels by deubiquitination effects."

sparser
"OTUD1 interacts with Smurf1 and functions as a deubiquitinase to remove the K48-linked ubiquitination of Smurf1, prevent its self-ubiquitination degradation, and upregulate its protein level; whereas the binding of Ndfip1 to MAVS recruits Smurf1 to MAVS, and the interaction between Ndfip1 and Smurf1 enhances the self-ubiquitination (possibly k63-linked) and enzyme activity of Smurf1 ( xref ) ( xref , xref )."

No evidence text available

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reach
"We found that SeV infection promoted interaction between OTUD1 and Smurf1 (XREF_FIG)."

sparser
"RNA virus infection promotes the interaction between OTUD1 and Smurf1, and binding of Smurf1 to MAVS/TRAF3/TRAF6."
SMURF1 activates OTUD1.
| 1
SMURF1 activates OTUD1. 1 / 1
| 1

reach
"Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG)."
OTUD1 affects YAP1
4 | 2 7
OTUD1 binds YAP1.
4 | 1 5
4 | 1 5

sparser
"OTUD1 binds to YAP and removes its K63-ubiquitin chain in a Hippo-independent manner, indicating that OTUD1 is a negative regulator of YAP signaling."

reach
"OTUD1 binds to YAP and removes its K63-ubiquitin chain in a Hippo-independent manner, indicating that OTUD1 is a negative regulator of YAP signaling."

No evidence text available

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sparser
"OTUD1 binds YAP and reverses its K63 ubiquitination."

sparser
"This non-proteolytic ubiquitination can be reversed by the binding and interaction between deubiquitinase OTUD1 and YAP1; OTUD1 decreases YAP1 stability, and attenuates the cell proliferation and tumor-growth activity of YAP1 ( xref )."

sparser
"We further validated the interaction between OTUD1 and YAP in vivo and in vitro."

sparser
"Moreover, His-YAP protein purified from bacteria could be pulled down by GST-OTUD1, but not by GST, in an in vitro binding assay (Fig.  xref ), suggesting that OTUD1 directly interacts with YAP."
OTUD1 ubiquitinates YAP1.
| 2
OTUD1 ubiquitinates YAP1. 2 / 2
| 2

sparser
"To further determine whether OTUD1 directly deubiquitinates YAP, we incubated purified OTUD1 and ubiquitinated YAP in a cell-free system."

sparser
"Using both the K63-specific mutant and the K63R mutant of ubiquitin, we found that of these four YAP-interacting DUBs, only OTUD1 clearly reduced K63-linked ubiquitination of YAP (Supplementary Fig.  xref ), while the other three DUBs (JOSD2, OTUD7B, and YOD1) substantially reduced non-K63-linked ubiquitination of YAP (Supplementary Fig.  xref )."
OTUD1 increases the amount of YAP1.
| 1
OTUD1 increases the amount of YAP1. 1 / 1
| 1

reach
"The slowed degradation of Nrf2 and YAP with the high expression of USP17 and OTUD1 was detected in the chemoresistant PDAC cell line, and the knockdown of OTUD1 reduced the levels of Nrf2 and YAP, and cell growth."
| 13
| 11

reach
"Moreover, ectopic expression of OTUD1 significantly inhibited metastasis in control cells but did not show significant inhibitory effect in the SMAD7 knockout cells."

reach
"Relatively, OTUD1 also can inhibit tumor metastasis by preventing the degradation of SMAD family member 7 (SMDA7), which can inhibit tumor metastasis by blocking TGF-β signaling pathway (Zhang et al., 2017)."

reach
"Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7."

reach
"Importantly, OTUD1 is lost in multiple types of human cancers and loss of OTUD1 increases metastasis in intracardial xenograft and orthotopic transplantation models, and correlates with poor prognosis among breast cancer patients."

reach
"Thus, OTUD1 represses breast cancer metastasis by mitigating TGF-beta-induced pro oncogenic responses via deubiquitination ofSMAD7."

reach
"OTUD1 inhibits metastasis in transplantable mouse models."

reach
"Taken together, these analyses show that loss of OTUD1 strongly promotes breast cancer lung metastasis."

reach
"Therefore, our studies suggest that OTUD1 inhibits lung metastasis in transplantable mouse models."

reach
"OTUD1 inhibits breast cancer metastasis by reducing TGF-β-induced tumor-promoting responses by deubiquitinating SMAD7 [7]."

reach
"Although cell transplantation induced bone metastasis to similar levels around day 21 post-injection, expression of OTUD1 wild-type (wt) beginning at day 21 significantly suppressed metastasis around day 35, which also led to increased mice survival."
| 2

reach
"OTUD1 is a deubiquitinase and among its targets is SMAD7, and OTUD1 deficiency destabilizes SMAD7 and potentiates TGF-beta1-driven metastasis [XREF_BIBR]."

reach
"However, knockdown of either OTUD1 or FGL1 in MC38 cells reduced hepatic metastases, which could be rescued by overexpressing rFGL1, indicating the critical role of FGL1 in TNFα-mediated progression of metastatic tumors (Fig. 6A, B)."
OTUD1 affects MCL1
2 1 | 2 8
OTUD1 binds MCL1.
2 | 2 8
2 | 2 8

sparser
"The immunoprecipitation was used to determine the interaction between OTUD1 and MCL1."

sparser
"OTUD1 interacts with MCL1 and promotes its deubiquitination."

sparser
"OTUD1 interacts with MCL1 and promotes MCL1 deubiquitination."

sparser
"We also found that OTUD1 interacted with MCL1 and removed the ubiquitin chain from it."

sparser
"These results indicate that OTUD1 interacts with MCL1 and regulates its stability through deubiquitination."

reach
"The immunoprecipitation was used to determine the interaction between OTUD1 and MCL1."

reach
"OTUD1 interacts with MCL1 and promotes its deubiquitination."

sparser
"Next, we tested whether OTUD1 interacts with MCL1."

sparser
"Since OTUD1 interacts with MCL1 and its enzymatic activity is required for MCL1 stability, then we tested whether OTUD1 influences the ubiquitination of MCL1."

No evidence text available
OTUD1 deubiquitinates MCL1.
1 |
OTUD1 deubiquitinates MCL1. 1 / 1
1 |

"The deubiquitinating enzyme <span class="match term0">OTUD1</span> antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the <span class="match term1">MCL1</span> protein"
OTUD1 affects KLF4
| 12 1
OTUD1 deubiquitinates KLF4.
| 6
OTUD1 deubiquitinates KLF4. 6 / 6
| 6

reach
"As shown in Figure 5e, OTUD1 overexpression notably repressed the polyubiquitination of KLF4 protein (Figure 5e)."

reach
"These findings suggest that OTUD1 deubiquitinated KLF4, thereby inhibiting KLF4 protein degradation."

reach
"41 , 48 We confirmed that OTUD1 obviously extended half‐lives of KLF4 and inhibited KLF4 ubiquitination level."

reach
"The deubiquitinase OTUD1 inhibits progression by deubiquitinating and stabilizing KLF4 in non-small cell lung cancer [10]."

reach
"OTUD1 was positively correlated with KLF4 and stabilized KLF4 at protein level by deubiquitinating KLF4."

reach
"OTUD1 stabilizes KLF4 by deubiquitinating KLF4 ."
OTUD1 inhibits KLF4.
| 3
OTUD1 inhibits KLF4. 3 / 3
| 3

reach
"Another study identified that the deubiquitinase OTUD1 suppressed tumor progression by stabilizing KLF4 in NSCLC cells [148] ."

reach
"Moreover, more studies need to be performed to determine whether OTUD1 exerts consistent roles in mice models.In conclusion, this investigation for the first time has elucidated that OTUD1 inhibits NSCLC cell progression including cell growth, migration and invasion by stabilizing and ubiqutinating the tumor suppressor, KLF4."

reach
"OTUD1 upregulation suppressed cell viability and invasion and migration via mediating stabilization of KLF4, while silencing of OTUD1 showed the opposite effect [148] ."
OTUD1 activates KLF4.
| 3
OTUD1 activates KLF4. 3 / 3
| 3

reach
"Nevertheless, knockdown of OTUD1 dramatically reduced the KLF4 half‐lives (Figure 5c,d), which suggested that OTUD1 reduced the degradation of KL4."

reach
"The results illustrated that OTUD1 overexpression increased KLF4 protein levels while OTUD1 knockdown remarkably decreased the protein load of KLF4."

reach
"However, OTUD1 did not significantly affect KLF4 mRNA expression in PC9 cells (Figure 4c,d), implying that OTUD1 might mediate the post‐translational modification of KLF4."
OTUD1 binds KLF4.
| 1
| 1

sparser
"For example, we did not verify whether OTUD1 interacts with KLF4 directly and confirm the ubiquitination site of KLF4."
OTUD1 affects Hypertrophy
| 13
OTUD1 activates Hypertrophy.
| 11
| 11

reach
"OTUD1 deficiency attenuated myocardial hypertrophy and cardiac dysfunction induced by ISO infusion or MI operation."

reach
"The macrophage inflammation mediated by the ISO‐OTUD1‐CARD9 axis further promotes hypertrophy and fibrosis in cardiomyocytes and fibroblasts, respectively, inducing cardiac remodelling."

reach
"m6A modification leads to OTUD1 upregulation in cardiac hypertrophy."

reach
"Wang et al. demonstrated that OTUD1 promoted the development of pathological myocardial hypertrophy by removing the K63-linked ubiquitin chains of STAT3 and stabilizing the protein in various rodent models of myocardial hypertrophy."

reach
"OTUD1 deficiency prevents TAC-induced myocardial hypertrophy and fibrosis."

reach
"We speculated that OTUD1 might promote cardiac hypertrophy by activating MAPK signaling."

reach
"these results confirm that OTUD1 deficiency suppresses deleterious myocardial hypertrophy and fibrosis."

reach
"These results show that OTUD1 is needed for Ang II to induce hypertrophy and expression of fibrotic factors in cardiomyocytes."

reach
"OTUD1 promotes Cardiac Hypertrophy in an ASK1-Dependent Manner."

reach
"Our group has recently found that cardiomyocyte OTUD1 promoted angiotensin II‐ and TAC‐driven cardiac dysfunction, hypertrophy and fibrosis, while the role of OTUD1 was evaluated using the whole‐body OTUD1 knockout mice but not the myocardial‐specific OTUD1 knockout mice or BMT."
OTUD1 inhibits Hypertrophy.
| 2
| 2

reach
"OTUD1 deficiency prevents TAC-induced myocardial hypertrophy and fibrosis."

reach
"OTUD1 knockout alleviates TAC-induced Cardiac Hypertrophy in Mice."
MAP3K5 affects OTUD1
| 6 7
MAP3K5 binds OTUD1.
| 4 7
| 4 7

sparser
"Then, we proceeded to investigate the in vivo function of the Otud1-Ask1 axis."

sparser
"OTUD1 physically interacts with ASK1 and is involved in MAPK pathway regulation, which is essential for the maintenance of CSC properties (Fig.  xref )."

sparser
"We then examined the interaction between OTUD1 and ASK1."

sparser
"Reciprocal coimmunoprecipitation (Co-IP) revealed that OTUD1 binds to ASK1 (Fig.  xref ), and their interaction was not influenced by the enzymatically inactive OTUD1 C320A mutant (Fig.  xref )."

sparser
"As shown in Fig.  xref h, both the N-terminus and C-terminus of OTUD1 bound to ASK1."

reach
"We then examined the interaction between OTUD1 and ASK1."

reach
"Reciprocal coimmunoprecipitation (Co-IP) revealed that OTUD1 binds to ASK1 (Fig. 2e), and their interaction was not influenced by the enzymatically inactive OTUD1 C320A mutant (Fig. 2f)."

sparser
"OTUD1 is involved in MAPK/JNK pathway regulation and physically interacts with ASK1."

reach
"Because OTUD1 strongly bound to ASK1, we sought to determine whether ASK1 could be recruited to OTUD1-based aggresomes."

reach
"As shown in Fig. 2g, h, both the N-terminus and C-terminus of OTUD1 bound to ASK1."
MAP3K5 activates OTUD1.
| 2
MAP3K5 activates OTUD1. 2 / 2
| 2

reach
"ASK1/JNK pathway inhibitors effectively suppressed OTUD1-mediated OSCS."

reach
"These results indicate that ASK1 mediates the exacerbation role of OTUD1 in cardiac hypertrophy."
STAT3 affects OTUD1
| 3 9
| 3 9

sparser
"These in vitro studies show that OTUD1 interacts with STAT3 and regulates Tyr-705 phosphorylation and nuclear translocation to module expression of cardiac remodeling genes."

sparser
"These results indicate that STAT3 binds to OTUD1 directly via STAT3 SH2 domain."

sparser
"After identifying STAT3-OTUD1 interaction site, we mutated active sites on OTUD1 (cysteine at position 320 to serine) (Figure xref E)."

sparser
"Mechanistically, we showed that OTUD1 binds to STAT3 and causes deubiquitination of STAT3."

sparser
"This study further elucidated that OTUD1 bound to the SH2 domain of STAT3 through its cysteine site at position 320, thereby exerting the effect of deubiquitination (Ref. xref )."

reach
"To confirm this potential interaction between OTUD1 and STAT3, we transfected NVRMs and HEK-293T cells with Flag-tagged OTUD1 and showed that STAT3 interacts with OTUD1 following co-IP assay (Figure 5C-D)."

reach
"We tested the idea that OTUD1 binding to STAT3 may disrupt STAT3-KPNA3 association, which possibly reduces nuclear translocation."

reach
"Mechanistically, we showed that OTUD1 binds to STAT3 and causes deubiquitination of STAT3."

sparser
"Our detailed mechanistic studies showed that OTUD1 interacts with signal transducer and activator of transcription 3 (STAT3) and leads to deubiquitination and increased phosphorylation of STAT3."

sparser
"OTUD1 interacts directly with STAT3 and promotes STAT3 activation."
RIPK2 affects OTUD1
| 2 10
| 2 10

sparser
"Strikingly, our findings revealed that OTUD1 interacted with RIP2 through the kinase domain or CARD domain and removed its K63-linked polyubiquitin chains, resulting in the inhibition of RIP2-induced NF-κB activation in cerebral ischemic lesion."

sparser
"Overall, our study proposed a model for OTUD1RIP2 interaction and function in cerebral ischemia."

sparser
"Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1."

sparser
"Mechanistically, OTUD1 interacted with RIP2 and sequentially removed the K63-linked polyubiquitin chains of RIP2, thereby inhibiting NF-κB activation."

sparser
"OTUD1 interacted with RIP2."

sparser
"Given the OTUD1 and RIP2 protein expression were both elevated and localized in microglia and astrocytes of mice with cerebral ischemia, we hypothesize that OTUD1 interacted with RIP2, thus regulate the ubiquitination of RIP2."

sparser
"The endogenous interaction between OTUD1 and RIP2 was determined by Co-IP and immunofluorescence in BV2 cells subjected to OGD/R injury."

sparser
"To dig out the necessary domains of RIP2 interaction with OTUD1, a series of truncated mutants of RIP2 were transfected for Co-IP experiments."

reach
"Immunoprecipitation and confocal microscopy were used to study the interaction of RIP2 and OTUD1."

reach
"The endogenous interaction between OTUD1 and RIP2 was determined by Co-IP and immunofluorescence in BV2 cells subjected to OGD/R injury."
OTUD1 affects IREB2
| 11 1
OTUD1 deubiquitinates IREB2.
| 7
OTUD1 deubiquitinates IREB2. 7 / 7
| 7

reach
"OTUD1 prevents ferroptosis by deubiquitinating and stabilizing IREB2."

reach
"Thus, targeting CD36 can reshape the composition and function of T cells in the TME through the ferroptosis pathway.The ovarian tumor domain-containing protein 1 (OTUD1) is involved in the deubiquitination of iron-responsive element-binding protein 2 (IREB2), stabilizing IREB2 to enhance iron transport mediated by transferrin receptor 1 (TFR1)."

reach
"OTUD1 was also shown to exacerbate colon cancer progression by deubiquitinating and stabilizing iron-responsive element-binding protein 2 (IREB2) , indicating that OTUD1 could act as an oncogene."

reach
"Song et al. found that overexpression of OTUD1 inhibits the ubiquitination and degradation of iron-responsive element-binding protein 2 (IREB2) in colorectal cancer cells."

reach
"143 OTUD1 promotes the deubiquitination of IREB2, which inhibits the degradation of IREB2 protein and activates the expression of TFRC, thereby increasing the concentration of iron ions in tumor cells and enhancing the sensitivity to ferroptosis as well as the infiltration of CD8+ T cells, improving antitumor immune response."

reach
"In contrast, OTUD1 is specifically down-regulated in CRC, resulting in hyperubiquitination of its downstream protein, IRP2, promoting its degradation, and reducing iron uptake by CRC cells via TfR1 ( Figure 3 ) (8).4 Genes associated with CRC."

reach
"OTUD1 stimulates ROS generation and ferroptosis by deubiquitinating and stabilizing IREB2 and promoting iron transportation."
OTUD1 binds IREB2.
| 1 1
| 1 1

reach
"Studies have shown that in colon cancer, OTUD1 can bind and promote the deubiquitination modification of IREB2 (iron-responsive element-binding protein2), a primary regulator of iron metabolism."

sparser
"Song et al. showed that OTUD1 binds IREB2 through the N-terminal APGR, and deubiquitinates K48- and K63-linked ubiquitin chains from IREB2."
OTUD1 activates IREB2.
| 2
OTUD1 activates IREB2. 2 / 2
| 2

reach
"OTUD1 promotes transferrin receptor protein 1 (TFRC)-mediated iron transport through deubiquitination and stabilization of IREB2, leading to increased ROS production and ferroptosis."

reach
"For example, OTUD1 has been shown to enhances iron transport and potentiate antitumor immunity in colon cancer by targeting/regulating iron-responsive element-binding protein 2 33."
OTUD1 ubiquitinates IREB2.
| 1
OTUD1 ubiquitinates IREB2. 1 / 1
| 1

reach
"OTUD1 prevents ferroptosis by deubiquitinating and stabilizing IREB2."
MCL1 affects OTUD1
2 | 2 8
2 | 2 8

sparser
"The immunoprecipitation was used to determine the interaction between OTUD1 and MCL1."

sparser
"OTUD1 interacts with MCL1 and promotes its deubiquitination."

sparser
"OTUD1 interacts with MCL1 and promotes MCL1 deubiquitination."

sparser
"We also found that OTUD1 interacted with MCL1 and removed the ubiquitin chain from it."

sparser
"These results indicate that OTUD1 interacts with MCL1 and regulates its stability through deubiquitination."

reach
"The immunoprecipitation was used to determine the interaction between OTUD1 and MCL1."

reach
"OTUD1 interacts with MCL1 and promotes its deubiquitination."

sparser
"Next, we tested whether OTUD1 interacts with MCL1."

sparser
"Since OTUD1 interacts with MCL1 and its enzymatic activity is required for MCL1 stability, then we tested whether OTUD1 influences the ubiquitination of MCL1."

No evidence text available
PRDX4 affects OTUD1
4 | 2 5
4 | 2 5

sparser
"To map and localize the OTUD1-PRDX4 interaction, we used the full length (FL) and the Δ1-38 PRDX4 constructs."

sparser
"However, a precise mechanism how OTUD1-PRDX4 axis mediates the Ig synthesis remained unclear."

No evidence text available

sparser
"In summary, our work unveils the OTUD1-PRDX4 axis as a yet undescribed regulatory pathway driving Ig production and PI sensitivity in MM cells and highlights importance of OTUD1 in myeloma proliferation (Fig.  xref )."

reach
"At the same time, OTUD1 binds and elevates PRDX4 protein amount."

reach
"Co-immunoprecipitation of OTUD1 and PRDX4 complexes was performed by lysing RPMI8226 cells in immunoprecipitation buffer (20 mM TRIS, pH 7.5, 150 mM NaCl, 0.5% NP40) containing phosphatase and protease inhibitor cocktail (Thermo Fisher Scientific), 20 mM N-ethylmaleimide, and 5 mM iodacetamide for 1 h on ice."

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No evidence text available

sparser
"Initially, we validated the OTUD1-PRDX4 interaction in series of reciprocal co-immunoprecipitations with both tagged and endogenous proteins (Fig.  xref )."
OTUD1 affects Fibrosis
| 11
OTUD1 activates Fibrosis.
| 8
| 8

reach
"Similarly, Picro Sirius Red and Masson's Trichrome staining revealed that OTUD1 knockout mice have reduced fibrosis compared to wildtype mice (Figure 2J-K, Figure S2G-L)."

reach
"OTUD1 deficiency prevents TAC-induced myocardial hypertrophy and fibrosis."

reach
"these results confirm that OTUD1 deficiency suppresses deleterious myocardial hypertrophy and fibrosis."

reach
"Otud1 knockout significantly ameliorated Ang II-induced HRD, whereas OTUD1 overexpression exacerbated Ang II-induced kidney damage and fibrosis."

reach
"OTUD1 and USP22 have been shown to promote fibrosis and injury in renal tubular epithelial cells ."

reach
"Our group has recently found that cardiomyocyte OTUD1 promoted angiotensin II‐ and TAC‐driven cardiac dysfunction, hypertrophy and fibrosis, while the role of OTUD1 was evaluated using the whole‐body OTUD1 knockout mice but not the myocardial‐specific OTUD1 knockout mice or BMT."

reach
"OTUD1 increases Ang II-induced cardiomyocyte myocardial hypertrophy and fibrosis by regulating STAT3."

reach
"The macrophage inflammation mediated by the ISO‐OTUD1‐CARD9 axis further promotes hypertrophy and fibrosis in cardiomyocytes and fibroblasts, respectively, inducing cardiac remodelling."
OTUD1 inhibits Fibrosis.
| 3
| 3

reach
"OTUD1 deficiency promoted angiogenesis and fibrosis in wound tissues of T1DM and T2DM mice and alleviated HG + "

reach
"Moreover, the obtained results demonstrated that OTUD1 inhibited the expression of fibrosis-related proteins in HEMCs in vitro, and the mechanistic execution of this phenotype was achieved via coordinated deubiquitination coupled with MADH7-mediated transcriptional reprogramming."

reach
"OTUD1 deficiency prevents TAC-induced myocardial hypertrophy and fibrosis."
IRF3 affects OTUD1
5 | 1 5
5 | 5

sparser
"Subsequent co-immunoprecipitation assay verified the association of OTUD1 with IRF3 ( Fig. 3 B)."

sparser
"In addition to T407P and G430V which are assumed to neutral mutations, other OTUD1 mutants impair its suppressive effects on innate immunity through blocking the association of OTUD1 with IRF3 or dire[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

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sparser
"In addition to its role in T cell activation and function, FOXO3 elicits an inhibitory effect on the innate immune response through activation of OTUD1-IRF3 signaling."

No evidence text available

sparser
"OTUD1 interacts with IRF3 to remove the K63-linked poly-ubiquitin chains on IRF3 and to suppress the interferon activity."

sparser
"We next used immunofluorescence assays to confirm the association of OTUD1 with IRF3."

No evidence text available
OTUD1 binds IRF3 and K63. 1 / 1
| 1

reach
"As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63 linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity."
YAP1 affects OTUD1
4 | 1 5
4 | 1 5

sparser
"OTUD1 binds to YAP and removes its K63-ubiquitin chain in a Hippo-independent manner, indicating that OTUD1 is a negative regulator of YAP signaling."

reach
"OTUD1 binds to YAP and removes its K63-ubiquitin chain in a Hippo-independent manner, indicating that OTUD1 is a negative regulator of YAP signaling."

No evidence text available

No evidence text available

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sparser
"OTUD1 binds YAP and reverses its K63 ubiquitination."

sparser
"This non-proteolytic ubiquitination can be reversed by the binding and interaction between deubiquitinase OTUD1 and YAP1; OTUD1 decreases YAP1 stability, and attenuates the cell proliferation and tumor-growth activity of YAP1 ( xref )."

sparser
"We further validated the interaction between OTUD1 and YAP in vivo and in vitro."

sparser
"Moreover, His-YAP protein purified from bacteria could be pulled down by GST-OTUD1, but not by GST, in an in vitro binding assay (Fig.  xref ), suggesting that OTUD1 directly interacts with YAP."
PGAM5 affects OTUD1
1 | 4 5
1 | 3 5

sparser
"The binding of Pgam5 and Otud1 was validated by both exogenous and endogenous immunoprecipitation."

reach
"The binding of Pgam5 and Otud1 was validated by both exogenous and endogenous immunoprecipitation."

reach
"This upregulated OTUD1 then interacts with and deubiquitinates PGAM5, promoting ASK1 phosphorylation and the activation of the p38/JNK MAPK signaling pathway."

No evidence text available

sparser
"Therefore, our findings showed that OTUD1 interacts with PGAM5 and promotes its ubiquitination and degradation."

reach
"OTUD1 binds to and deubiquitinates PGAM5."

sparser
"OTUD1 binds to and deubiquitinates PGAM5."

sparser
"Conclusion : Our findings confirm that targeting the OTUD1-PGAM5 axis holds significant potential as a therapeutic approach for heart failure associated with pathological hypertrophy."

sparser
"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure xref C-D)."
OTUD1 binds PGAM5 and 293T. 1 / 1
| 1

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"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure 6C-D)."
OTUD1 affects TYK2
| 8 2
OTUD1 binds TYK2.
| 2 2
| 2 2

reach
"Consistently, the spleen tissues of depression model mice displayed lower AHI1 levels and less interaction between OTUD1 and Tyk2 than those of normal mice (Fig. 4h)."

reach
"We noticed that AHI1 did not strongly affect OTUD1 protein levels (Fig. 4f) but affected the interaction between OTUD1 and Tyk2, as shown by the abolishment of the OTUD1-Tyk2 interaction upon AHI1 knockout in primary macrophages (Fig. 4g)."

sparser
"We noticed that AHI1 did not strongly affect OTUD1 protein levels (Fig.  xref ) but affected the interaction between OTUD1 and Tyk2, as shown by the abolishment of the OTUD1-Tyk2 interaction upon AHI1 knockout in primary macrophages (Fig.  xref )."

sparser
"Consistently, the spleen tissues of depression model mice displayed lower AHI1 levels and less interaction between OTUD1 and Tyk2 than those of normal mice (Fig.  xref )."
OTUD1 increases the amount of TYK2.
| 3
OTUD1 increases the amount of TYK2. 3 / 3
| 3

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"Importantly, AHI1 deficiency inhibited OTUD1-mediated both downregulation of Tyk2 ubiquitination (Fig. 5c) and upregulation of Tyk2 protein levels (Supplementary information, Fig. S5g), suggesting that OTUD1 regulates Tyk2 ubiquitination and protein levels dependently on AHI1.OTUD1 has been reported to be able to regulate both K48-linked and K63-linked ubiquitination of protein substrates."

reach
"We found that OTUD1 overexpression increased Tyk2 protein levels in a dose-dependent manner (Supplementary information, Fig. S5b), while OTUD1 knockout in primary macrophages dramatically reduced Tyk2 protein levels (Fig. 4d)."

reach
"Importantly, OTUD1 knockdown inhibited the AHI1-mediated upregulation of Tyk2 levels (Fig. 4e), suggesting that OTUD1 is essential for the AHI1-mediated regulation of Tyk2 protein levels."
OTUD1 deubiquitinates TYK2.
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OTUD1 leads to the deubiquitination of TYK2. 1 / 1
| 1

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"In line with this, OTUD1 deficiency in both primary macrophages (Fig. 5b) and MEFs (Supplementary information, Fig. S5d), as well as A549 cells (Supplementary information, Fig. S5e), markedly improved Tyk2 ubiquitination levels, whereas OTUD1 overexpression inhibited Tyk2 ubiquitination (Fig. 5c; Supplementary information, Fig. S5f)."
OTUD1 decreases the amount of TYK2.
| 1
OTUD1 decreases the amount of TYK2. 1 / 1
| 1

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"We found that OTUD1 overexpression increased Tyk2 protein levels in a dose-dependent manner (Supplementary information, Fig. S5b), while OTUD1 knockout in primary macrophages dramatically reduced Tyk2 protein levels (Fig. 4d)."
OTUD1 activates TYK2.
| 1
OTUD1 activates TYK2. 1 / 1
| 1

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"It will be interesting to clarify the signaling crosstalk between different types of cells stimulated by different hormones in the future.In summary, we found that depression-elevated AVP induces AHI1 reduction in macrophages, which further disrupts the deubiquitinase OTUD1-mediated stabilization of cellular Tyk2, thus attenuating basal IFN-I signaling and host antiviral immune defense (Fig. 8h)."
OTUD1 affects TRAF6
| 7 3
OTUD1 decreases the amount of TRAF6.
| 4
OTUD1 decreases the amount of TRAF6. 3 / 3
| 3

reach
"In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6."

reach
"OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."

reach
"Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."
Modified OTUD1 decreases the amount of TRAF6. 1 / 1
| 1

reach
"Similarly, OTUD1 overexpression lowered protein levels of TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG)."
OTUD1 binds TRAF6.
| 1 3
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
| 1

reach
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
OTUD1 inhibits TRAF6.
| 2
OTUD1 inhibits TRAF6. 2 / 2
| 2

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"Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG)."

reach
"In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited."
OTUD1 affects TRAF3
| 7 3
OTUD1 binds TRAF3.
| 1 3
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
| 1

reach
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
OTUD1 inhibits TRAF3.
| 3
OTUD1 inhibits TRAF3. 2 / 2
| 2

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"In the presence of MG132, the ability of OTUD1 to downregulate MAVS (XREF_FIG), or TRAF3 (XREF_FIG), or TRAF6 (XREF_FIG) was largely inhibited."

reach
"Interestingly, Smurf1 knockdown also remarkably blocked OTUD1 mediated downregulation of both TRAF3 (XREF_FIG) and TRAF6 (XREF_FIG)."
Modified OTUD1 inhibits TRAF3. 1 / 1
| 1

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"However, we noticed that OTUD1 overexpression gradually downregulated the levels of MAVS, TRAF3, and TRAF6 (XREF_FIG), which is consistent with the observation that OTUD1 overexpression inhibits the induction of type I IFNs and proinflammatory cytokines."
OTUD1 decreases the amount of TRAF3.
| 3
OTUD1 decreases the amount of TRAF3. 3 / 3
| 3

reach
"In this study, we uncovered that OTUD1 can downregulate protein levels of MAVS, TRAF3 and TRAF6."

reach
"OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."

reach
"Together, these data suggest that OTUD1 negatively regulates protein levels of MAVS, TRAF3, and TRAF6."
OTUD1 affects Flag
| 10
| 10

sparser
"GST‐tagged AIF was confirmed to be directly associated with FlagOTUD1, and vice versa (Figure  xref )."

sparser
"We transfected NVRMs with Flag-OTUD1 to express OTUD1 and then challenged the cells with Ang II in the presence or absence of STAT3 inhibitor."

sparser
"Furthermore, His-RIP2 and Flag-OTUD1 were transfected into HEK293T cells, Co-IP experiment and confocal microscopy observed the interaction and colocalization of His-RIP2 with Flag-OTUD1 (Fig.  xref C, D)."

sparser
"MS was performed as previously described. [ xref ] Briefly, FlagOTUD1 was transfected into 293T cells, and cell lysates were immunoprecipitated with anti‐Flag magnetic beads."

sparser
"U2OS, HCT116, or 293T cells were transfected with vectors expressing Flag-OTUD1, HA-Ub, or Myc-p53, as indicated."

sparser
"p53 was specifically immunoprecipitated with OTUD1 by the Flag M2 bead in U2OS cells overexpressed with Flag-OTUD1 and Myc-p53 ( Fig. 3 A )."

sparser
"Further, p53 was also specifically immunoprecipitated with OTUD1 by the p53 antibody, but not control IgG, in U2OS cells overexpressed with Flag-OTUD1 ( Fig. 3 B)."

sparser
"No notable changes were observed in the degradation rate of CARD9 protein in HEK‐293T transfected with FlagOTUD1 (Figure  xref )."

sparser
"Overexpressing FlagOTUD1 in HEK 293T cells did not increase the protein level of CARD9 (Figure  xref )."

sparser
"Neither overexpression of OTUD1 by transfected Flag-OTUD1 nor knockdown of OTUD1 by siRNA in HEK293T cells showed any significant change in protein level of RIP2, indicating OTUD1 did not affect RIP2 protein degradation (Fig.  xref C, D)."
| 8
| 4
Mutated OTUD1 inhibits immune response. 2 / 2
| 2

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"Our data demonstrate that OTUD1 is involved in maintaining immune homeostasis and loss-of-function mutations of OTUD1 enhance the immune response and are associated with autoimmunity."

reach
"Meanwhile, previous studies have demonstrated that Otud1 knockout mice were more susceptible to lipopolysaccharide (LPS)-induced sepsis [11], and loss-of-function mutations of OTUD1 enhanced immune response and were associated with autoimmunity [12], suggesting a potential role for OTUD1 in hepatic inflammation caused by I/R."

reach
"Additionally, OTUD1 and FGL1 depletion significantly restored TNFα-reduced anticancer immunity and prolonged the OS of mice stimulated with TNFα (Fig. 6C, D, S5D), consistent with the above in vitro findings."

reach
"For example, USP3 and CYLD were reported to negatively regulate type I IFN induction by targeting RIG-I ( Cui et al., 2014 ; Friedman et al., 2008 ); OTUD1 potently inhibits innate antiviral immunity [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD1 activates immune response.
| 4

reach
"At the same time, OTUD1 also increases the release of damage-related molecular patterns (DAMPs) to recruit white blood cells and enhance the host immune response."

reach
"The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity."

reach
"For example, OTUD1 has been shown to enhances iron transport and potentiate antitumor immunity in colon cancer by targeting/regulating iron-responsive element-binding protein 2 33."

reach
"A previous study showed that OTUD1 enhances iron transport and potentiates host antitumor immunity in colon cancer ."
OTUD1 affects TGFB
| 1 7
OTUD1 inhibits TGFB.
| 1 6
OTUD1 inhibits TGFB. 7 / 7
| 1 6

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"OTUD1 causes suppression of TGF-beta downstream signals and EMT."

eidos
"Moreover , OTUD1 suppresses TGF-beta signaling and EMT in MCF10A cells expressing RAS and metastasis of breast cancer cells in mice , respectively , presumably through deubiquitylating SMAD7 thus enabling SMURF2 binding and subsequent TGFR turnover43 ."

reach
"We next investigated the molecular mechanism by which OTUD1 inhibits TGF-beta and SMAD signaling."

reach
"Ectopic expression of OTUD1 could suppress TGF-beta signaling in control cells but barely showed effect in SMAD7 deficient cells; also knockdown of OTUD1 could promote TGF-beta signaling in control cells but not in SMAD7 deficient cells, suggesting thatinhibitory SMAD7 might be the major target of OTUD1 in the TGF-beta pathway."

reach
"For instance, deubiquitination of FOXM1 induces cancer progression and chemoresistance through the DUB UCHL3; OTUD1 reduces the pro-oncogenic TGF-β signaling mediated by SMAD7 to suppress the metastasis in breast cancer [93,94]."

reach
"In this model, OTUD1 represses breast cancer metastasis by mitigating TGF-β activity and loss of OTUD1 in aggressive forms derives TGF-β signaling and metastasis."

reach
"It was reported that OTUD1 could specifically inhibit transforming growth factor-beta (TGF-β) signaling in breast cancer metastasis by empowering SMAD7 [11]."
OTUD1 deubiquitinates TGFB.
| 1
OTUD1 deubiquitinates TGFB. 1 / 1
| 1

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"Further investigation reveals that OTUD1 directly deubiquitinates the TGF-beta pathway inhibitor SMAD7 and prevents its degradation."
OTUD1 affects SMAD3
3 | 4 1
OTUD1 binds SMAD3.
3 | 1 1
3 | 1 1

sparser
"FLAG–OTUD1-pulldown assays followed by mass spectrometric analyses of human umbilical vein endothelial cells suggest that SMAD3 binds OTUD1."

reach
"FLAG–OTUD1-pulldown assays followed by mass spectrometric analyses of human umbilical vein endothelial cells suggest that SMAD3 binds OTUD1."

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OTUD1 deubiquitinates SMAD3.
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OTUD1 deubiquitinates SMAD3. 2 / 2
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"Our findings demonstrate that endothelial OTUD1 promotes Ang II-induced vascular remodeling by deubiquitinating SMAD3."

reach
"Mouse endothelial OTUD1 promotes angiotensin II-induced vascular remodeling by deubiquitinating SMAD3."
OTUD1 inhibits SMAD3.
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OTUD1 inhibits SMAD3. 1 / 1
| 1

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"OTUD1 downregulation attenuated vascular remodeling, collagen deposition, and EndMT by targeting SMAD3 20."
OTUD1 affects RIPK1
4 | 3 1
OTUD1 binds RIPK1.
4 | 1
4 | 1

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sparser
"The OTUD1-RIPK1 axis may be mediated by inhibiting NF-κB activation to regulate intestinal inflammation [ 38 ]."

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OTUD1 ubiquitinates RIPK1.
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OTUD1 ubiquitinates RIPK1. 1 / 1
| 1

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"For example, OTUD1 can inhibit colonic inflammation by deubiquitinating RIPK1 to suppress NF-κB signaling ."
OTUD1 inhibits RIPK1.
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OTUD1 inhibits RIPK1. 1 / 1
| 1

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"When treated with the DUB panel, OTUD1 substantially reduced HMW forms of RIP1, suggesting the prevalence of Lys63 linkages on RIP1."
OTUD1 deubiquitinates RIPK1.
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OTUD1 deubiquitinates RIPK1. 1 / 1
| 1

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"For example, OTUD1 can inhibit colonic inflammation by deubiquitinating RIPK1 to suppress NF-κB signaling ."
METTL3 affects OTUD1
| 7 1
METTL3 activates OTUD1.
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METTL3 activates OTUD1. 5 / 5
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"This study showed that OTUD1 deubiquitinates PDE5A, leading to its stabilization and increased cGMP degradation, which exacerbates cardiac hypertrophy and heart failure 58.Our research advances the understanding of OTUD1's role in cardiac hypertrophy and remodeling by elucidating the specific molecular mechanism involving the METTL3-mediated m6A modification of OTUD1 mRNA."

reach
"These findings support the notion that METTL3-mediated m6A modification enhances the stability and expression of OTUD1 mRNA."

reach
"Moreover, YTHDF1 had a direct interaction with OTUD1 mRNA (Figure S4J), which was reduced or strengthened by the knockdown (Figure 3M) or overexpression (Figure S4K) of METTL3, respectively."

reach
"Specifically, we demonstrate that METTL3-mediated m6A modification enhances OTUD1 mRNA stability, leading to increased OTUD1 protein expression."

reach
"To further validate role of METTL3 mediated OTUD1 RNA modification in cardiac hypertrophy in vivo, we used METTL3 inhibitor (STM2457) to treat AAV9-Otud1 mice."
METTL3 increases the amount of OTUD1.
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METTL3 increases the amount of OTUD1. 2 / 2
| 2

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"METTL3 knockdown reduced m6A level of OTUD1 transcript (Figure 3E) and OTUD1 protein levels (Figure 3F) and its mRNA half-life (Figure 3H)."

reach
"YTHDF1 overexpression could restore the decreased protein expression of OTUD1 caused by silencing METTL3 (Figure S4L)."
METTL3 binds OTUD1.
| 1
| 1

sparser
"METTL3 could directly interact with OTUD1 mRNA (Figure xref D)."
BST2 affects OTUD1
| 2 6
| 2 6

sparser
"In addition, in this study, we only used labeled proteins to verify the interaction between OTUD1 and BST-2, and did not verify endogenous protein interaction or deeply explore the relationship between OTUD1, BST-2 and Vpu."

sparser
"While this mutation did not disrupt the interaction between OTUD1 and BST-2 ( xref D), it abolished the ability of OTUD1 to reduce BST-2 ubiquitination ( xref E,F)."

sparser
"In this study, we conducted a small interfering RNA (siRNA) screening of human DUBs and determined that OTUD1 interacts with BST-2, leading to a reduction in its K48- and K63-linked ubiquitination."

reach
"While this mutation did not disrupt the interaction between OTUD1 and BST-2 (Figure 4D), it abolished the ability of OTUD1 to reduce BST-2 ubiquitination (Figure 4E,F)."

reach
"In addition, in this study, we only used labeled proteins to verify the interaction between OTUD1 and BST-2, and did not verify endogenous protein interaction or deeply explore the relationship between OTUD1, BST-2 and Vpu."

sparser
"Notably, OTUD1 interacts with BST-2, reducing its K48- and K63-linked ubiquitination at Lys21, thereby stabilizing its surface expression."

sparser
"Co-immunoprecipitation showed that OTUD1 may interact with BST-2 protein ( xref A,B)."

sparser
"Collectively, these findings indicate that OTUD1 not only interacts with BST-2, but also plays a crucial role in regulating BST-2 protein levels."
SMAD7 affects OTUD1
5 | 2
5 | 2

sparser
"Moreover, Zhang et al. reported that OTUD1 binds with and stabilizes SMAD7 to repress the metastasis of breast cancer xref ."

sparser
"OTUD1 associates with SMAD7 and deubiquitinates SMAD7 in vitro."

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reach
"Moreover, more studies need to be performed to determine whether OTUD1 exerts consistent roles in mice models.In conclusion, this investigation for the first time has elucidated that OTUD1 inhibits NSCLC cell progression including cell growth, migration and invasion by stabilizing and ubiqutinating the tumor suppressor, KLF4."

reach
"OTUD1 overexpression inhibits NSCLC cell proliferation, migration and invasion."

reach
"Taken together, these results suggested that overexpression OTUD1 notably inhibits NSCLC cell progression including proliferation, migration and invasion."

reach
"OTUD1 knockdown promotes NSCLC cell proliferation, migration and invasion."

reach
"Transwell assay demonstrated that silencing OTUD1 significantly accelerated PC9 and A549 cell migration and invasion (p < 0.01, Figure 3c,d)."

reach
"OTUD1 upregulation suppressed cell viability and invasion and migration via mediating stabilization of KLF4, while silencing of OTUD1 showed the opposite effect [148] ."
| 1

reach
"In the LPS-induced ALI model, deficiency of OTUD1 significantly ameliorated pulmonary edema, reduced permeability damage, and decreased lung immunocyte infiltration."
OTUD1 affects Ad
| 7
| 7

sparser
"Otud1-overexpressing mice and control mice were generated by injecting recombinant adenovirus Ad-Otud1 or Ad-GFP into WT mice, followed by hepatic I/R operation."

sparser
"The recombinant adenovirus (Ad-Otud1) and the control adenovirus (Ad-GFP) were purchased from GeneChem (Shanghai, China)."

sparser
"Ad-GFP (5 × 10 9  pfu) or Ad-Otud1 (5 × 10 9  pfu) were injected into C5 7BL /6J WT mice via the tail vein at a volume of 125 μL 36 h before hepatic I/R operation [ xref ]."

sparser
"Figure xref Gdemonstrate that Ad-Otud1 increased the cell surface of NRCMs, while the cellular surface of cardiomyocytes was significantly reduced in the Ad-shOtud1 cell group (Figure xref H)."

sparser
"Primary hepatocytes were isolated from Nrf2-WT and Nrf2-KO mice, which were injected with Ad-GFP or Ad-Otud1 via tail vein and subjected to H/R treatment."

sparser
"To elucidate the regulatory mechanism of Otud1 in cardiac hypertrophy, RNA sequencing analyses of NRCMs infected with Ad-GFP and Ad-Otud1 were performed."

sparser
"Then, Otud1-expressing adenovirus (Ad-Otud1) and shRNA targeting Otud1 (Ad-shOtud1) were constructed to infect NRCMs."
OTUD1 affects AKT1
7 |
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OTUD1 is modified
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OTUD1 is ubiquitinated.
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OTUD1 is ubiquitinated. 6 / 6
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sparser
"Furthermore, we analyzed ubiquitination of endogenous Smurf1 in Otud1 +/+ and Otud1 -/- MEFs."

sparser
"The E3-ligase KEAP1 binds and ubiquitinates OTUD1."

sparser
"This ETGE-dependent interaction was validated by co-immunoprecipitation of endogenous proteins, along with KEAP1-mediated ubiquitination of OTUD1."

sparser
"KEAP1 mediated ubiquitination of OTUD1 had no influence on its levels, so the biological role of this interaction remained unclear [ xref ]."

sparser
"As expected, OTUD1 lacking the ETGE motif was less ubiquitinated compared to the wild type form (Fig.  xref ) suggesting that OTUD1 might be a target of the KEAP1 ubiquitin ligase activity."

sparser
"Using both the K63-specific mutant and the K63R mutant of ubiquitin, we found that of these four YAP-interacting DUBs, only OTUD1 clearly reduced K63-linked ubiquitination of YAP (Supplementary Fig.  xref ), while the other three DUBs (JOSD2, OTUD7B, and YOD1) substantially reduced non-K63-linked ubiquitination of YAP (Supplementary Fig.  xref )."
OTUD1 is degraded.
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OTUD1 is degraded. 1 / 1
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"YTHDF1 overexpression could restore the decreased protein expression of OTUD1 caused by silencing METTL3 (Figure S4L)."
NFE2L2 affects OTUD1
| 5 2
NFE2L2 binds OTUD1.
| 2 2
| 2 2

sparser
"Our findings demonstrated that the interaction between OTUD1 and NRF2 primarily occurred through its Neh2 domain (aa 1–111), as the Neh2 deletion truncation (NRF2-E) failed to bind with OTUD1 in HEK293T cells ( xref D)."

sparser
"Collectively, these results suggest a physical interaction between OTUD1 and NRF2."

reach
"Our findings demonstrated that the interaction between OTUD1 and NRF2 primarily occurred through its Neh2 domain (aa 1–111), as the Neh2 deletion truncation (NRF2-E) failed to bind with OTUD1 in HEK293T cells (Fig. 5D)."

reach
"Our mass spectrometric analysis reveals that OTUD1 binds KEAP1, a regulator of the transcription factor Nrf2, during ROS-induced oxidative stress [19] (Figure 5C)."
NFE2L2 activates OTUD1.
| 3
NFE2L2 activates OTUD1. 3 / 3
| 3

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"Our findings revealed that Nrf2 depletion abrogated the suppressive effect of Otud1 on apoptosis in H/R-treated primary hepatocytes (Fig. 4I and J)."

reach
"Nrf2 silence also nullified Otud1 activity in upregulating Ho-1 and Nqo1 proteins (Fig. S7B), as well as in downregulating ROS production under H/R treatment (Fig. S7C)."

reach
"In other words, NRF2 acts as a direct substrate of OTUD1 to mediate the anti-inflammatory and antioxidant effect of OTUD1 in hepatic I/R injury."
Ad affects OTUD1
| 7
| 7

sparser
"Otud1-overexpressing mice and control mice were generated by injecting recombinant adenovirus Ad-Otud1 or Ad-GFP into WT mice, followed by hepatic I/R operation."

sparser
"The recombinant adenovirus (Ad-Otud1) and the control adenovirus (Ad-GFP) were purchased from GeneChem (Shanghai, China)."

sparser
"Ad-GFP (5 × 10 9  pfu) or Ad-Otud1 (5 × 10 9  pfu) were injected into C5 7BL /6J WT mice via the tail vein at a volume of 125 μL 36 h before hepatic I/R operation [ xref ]."

sparser
"Figure xref Gdemonstrate that Ad-Otud1 increased the cell surface of NRCMs, while the cellular surface of cardiomyocytes was significantly reduced in the Ad-shOtud1 cell group (Figure xref H)."

sparser
"Primary hepatocytes were isolated from Nrf2-WT and Nrf2-KO mice, which were injected with Ad-GFP or Ad-Otud1 via tail vein and subjected to H/R treatment."

sparser
"To elucidate the regulatory mechanism of Otud1 in cardiac hypertrophy, RNA sequencing analyses of NRCMs infected with Ad-GFP and Ad-Otud1 were performed."

sparser
"Then, Otud1-expressing adenovirus (Ad-Otud1) and shRNA targeting Otud1 (Ad-shOtud1) were constructed to infect NRCMs."
AKT1 affects OTUD1
7 |
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reach
"OTUD1 may mediate the occurrence of stroke by activating the NF-kappaB signaling pathway in herpes simplex virus latent infection."

reach
"These results demonstrate that OTUD1 activates the ASK1-p38/JNK signaling pathway in response to pro-hypertrophy stimulation."

reach
"Therefore, we speculate that OTUD1 may mediate the occurrence of stroke in herpes simplex virus latent infection by activating the NF-κB signaling pathway."

reach
"Altogether, these findings illustrated that OTUD1 ameliorated brain ischemia by interacting with RIP2, which deubiquitinated of RIP2, and consequently repressed RIP2-induced NF-κB signaling pathway and downstream proinflammatory mediators."

reach
"Next, we investigated the specific signaling pathway activated by OTUD1 in hepatocytes under H/R exposure."
OTUD1 bound to PGAM5 activates signal transduction. 1 / 1
| 1

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"This upregulated OTUD1 then interacts with and deubiquitinates PGAM5, promoting ASK1 phosphorylation and the activation of the p38/JNK MAPK signaling pathway."

reach
"A recent report showed that OTUD1 inhibits colonic inflammation in vivo [28]."

reach
"OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling [ 20 ]."

reach
"Deubiquitinase (DUB)-mediated deubiquitination processes are closely associated with the occurrence and development of colonic inflammation.Previous study showed that the deubiquitinase OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling [11]."
| 3

reach
"Intriguingly, we provided direct evidence that OTUD1 interacted with RIP2 and cleaved its K63-linked polyubiquitin chains, rather than the K48-linked chains, which led to suppression of the RIP2-induced inflammatory response."

reach
"Myeloid-specific OTUD1 deletion also attenuated ISO-induced murine cardiac inflammation and remodelling."

reach
"Taken together, our findings suggested that targeting the OTUD1‐CARD9 axis has a protective effect against ISO‐driven cardiac inflammation and HF.Inflammation participates in the progression of ISO‐induced HF."
OTUD1 affects PTEN
| 1 5
OTUD1 binds PTEN.
| 5
| 5

sparser
"Therefore, the OTUD1PTEN axis suppresses tumor growth and regulates the resistance of ccRCC to tyrosine kinase inhibitors."

sparser
"First, the reciprocal immunoprecipitation assay indicated that endogenous OTUD1 interacts with PTEN in 786-O and ACHN cells (Fig. xref B, C)."

sparser
"Furthermore, OTUD1 interacts with PTEN and regulates its stability."

sparser
"Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs."

sparser
"OTUD1 negatively regulates the cell cycle to inhibit the abnormal proliferation of cancer cells, since OTUD1 interacts with phosphatase and tensin homolog (PTEN), a negative regulator of the AKT (also known as protein kinase B) and NF-κB signaling pathways, and regulates its stability ( xref C)."
OTUD1 deubiquitinates PTEN.
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OTUD1 deubiquitinates PTEN. 1 / 1
| 1

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"OTUD1 deubiquitinates and stabilizes PTEN, a well-known negative regulator of the PI3K/AKT/mTOR signaling pathway in ccRCC (Liu et al., 2022c)."
OTUD1 affects FGL1
| 6
OTUD1 activates FGL1.
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OTUD1 activates FGL1. 3 / 3
| 3

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"For example, OTUD1 can enhance the stability of fibrinogen-like protein 1 in liver microenvironment and thus regulate tumor progression via tumor associated macrophages-OTUD1- fibrinogen-like protein 1 axis (Li et al., 2023a); moreover, OTUD1 can serve a negative prognostic factor for hepatocellular carcinoma (Wu et al., 2019)."

reach
"However, knockdown of either OTUD1 or FGL1 in MC38 cells reduced hepatic metastases, which could be rescued by overexpressing rFGL1, indicating the critical role of FGL1 in TNFα-mediated progression of metastatic tumors (Fig. 6A, B)."

reach
"Mechanistically, tumor-associated macrophages (TAMs) activate NF-kB by secreting TNFalpha/IL-1beta in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination."
OTUD1 ubiquitinates FGL1.
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OTUD1 leads to the ubiquitination of FGL1. 1 / 1
| 1

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"Moreover, downregulation of OTUD1 abolished TAM-mediated deubiquitination of FGL1 and reduced TAM-induced FGL1 stabilization in MC38 and HT29 cells cultured with TAM-CM (Fig. 4H, I)."
OTUD1 inhibits FGL1.
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OTUD1 inhibits FGL1. 1 / 1
| 1

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"Consistently, half-life analysis using cycloheximide pulse-chase analysis showed that downregulation of OTUD1 attenuated the protein half-life of FGL1 in tumor cells cultured with TAM-CM (Fig. 4J)."
OTUD1 deubiquitinates FGL1.
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OTUD1 leads to the deubiquitination of FGL1. 1 / 1
| 1

reach
"We found that OTUD1 knockdown markedly increased the ubiquitination and degradation of FGL1 in MC38 and HT29 cells pretreated with Baf-A1 (Fig. 4D, E) and vice versa (Fig. 4F, G)."
| 6
| 6

reach
"Comprehensive histological analyses showed that OTUD1 expression enhances Ang II-responses manifesting as cardiac hypertrophy and fibrosis (Figure 7F-J, Figure S7E-O)."

reach
"These results demonstrate that OTUD1 promotes Ang II-induced cardiac remodeling and dysfunction through activating STAT3."

reach
"Our group has recently found that cardiomyocyte OTUD1 promoted angiotensin II‐ and TAC‐driven cardiac dysfunction, hypertrophy and fibrosis, while the role of OTUD1 was evaluated using the whole‐body OTUD1 knockout mice but not the myocardial‐specific OTUD1 knockout mice or BMT."

reach
"Conversely, increased expression of OTUD1 enhances Ang II-induced injuries in the heart."

reach
"OTUD1 increases Ang II-induced cardiomyocyte myocardial hypertrophy and fibrosis by regulating STAT3."

reach
"We also found that OTUD1 protein expression was elevated in Ang II-stimulated neonatal rat cardiac myocytes (NRCMs) (Figure 1F)."
OTUD1 affects AHI1
2 | 2 2
2 | 2 2

No evidence text available

No evidence text available

reach
"The authors report that AHI1 binds OTUD1, which then removes the K48-linked polyubiquitin chain from Tyk2 to escape from proteasomal degradation."

sparser
"Next, we confirmed the interaction between AHI1 and OTUD1, as well as Tyk2, in both primary macrophages (Fig.  xref ) and A549 cells (Supplementary information, Fig. S xref a)."

sparser
"The authors report that AHI1 binds OTUD1, which then removes the K48-linked polyubiquitin chain from Tyk2 to escape from proteasomal degradation."

reach
"Next, we confirmed the interaction between AHI1 and OTUD1, as well as Tyk2, in both primary macrophages (Fig. 4c) and A549 cells (Supplementary information, Fig. S5a)."
Bisphenol A affects OTUD1
5 |
Bisphenol A increases the amount of OTUD1.
3 |
Bisphenol A increases the amount of OTUD1. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
Bisphenol A decreases the amount of OTUD1.
2 |
Bisphenol A decreases the amount of OTUD1. 2 / 2
2 |

No evidence text available

No evidence text available
SMAD3 affects OTUD1
3 | 1 1
3 | 1 1

sparser
"FLAG–OTUD1-pulldown assays followed by mass spectrometric analyses of human umbilical vein endothelial cells suggest that SMAD3 binds OTUD1."

reach
"FLAG–OTUD1-pulldown assays followed by mass spectrometric analyses of human umbilical vein endothelial cells suggest that SMAD3 binds OTUD1."

No evidence text available

No evidence text available

No evidence text available
RIPK1 affects OTUD1
4 | 1
4 | 1

No evidence text available

No evidence text available

No evidence text available

sparser
"The OTUD1-RIPK1 axis may be mediated by inhibiting NF-κB activation to regulate intestinal inflammation [ 38 ]."

No evidence text available
PTEN affects OTUD1
| 5
| 5

sparser
"Therefore, the OTUD1PTEN axis suppresses tumor growth and regulates the resistance of ccRCC to tyrosine kinase inhibitors."

sparser
"First, the reciprocal immunoprecipitation assay indicated that endogenous OTUD1 interacts with PTEN in 786-O and ACHN cells (Fig. xref B, C)."

sparser
"Furthermore, OTUD1 interacts with PTEN and regulates its stability."

sparser
"Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs."

sparser
"OTUD1 negatively regulates the cell cycle to inhibit the abnormal proliferation of cancer cells, since OTUD1 interacts with phosphatase and tensin homolog (PTEN), a negative regulator of the AKT (also known as protein kinase B) and NF-κB signaling pathways, and regulates its stability ( xref C)."
OTUD1 affects type I IFNs
| 5
OTUD1 inhibits type I IFNs.
| 4
OTUD1 inhibits type I IFNs. 4 / 4
| 4

reach
"In the present study, we report that the OTU deubiquitinase 1 (OTUD1) negatively regulates RNA virus triggered production of type I IFNs and proinflammatory cytokines."

reach
"In a screen of deubiquitinases expression cloning library [XREF_BIBR, XREF_BIBR], we found that the deubiquitinase OTUD1 could inhibit RNA virus induced production of type I IFNs."

reach
"However, we noticed that OTUD1 overexpression gradually downregulated the levels of MAVS, TRAF3, and TRAF6 (XREF_FIG), which is consistent with the observation that OTUD1 overexpression inhibits the induction of type I IFNs and proinflammatory cytokines."

reach
"Consequently, OTUD1 negatively regulates RNA virus triggered production of type I IFNs and proinflammatory cytokines."
OTUD1 activates type I IFNs.
| 1
OTUD1 activates type I IFNs. 1 / 1
| 1

reach
"Following viral infection, OTUD1 knockout mice were shown to produce more type I IFNs and proinflammatory cytokines and were more resistant to lethal viral infection."
OTUD1 affects cell growth
| 5
| 5

reach
"Moreover, more studies need to be performed to determine whether OTUD1 exerts consistent roles in mice models.In conclusion, this investigation for the first time has elucidated that OTUD1 inhibits NSCLC cell progression including cell growth, migration and invasion by stabilizing and ubiqutinating the tumor suppressor, KLF4."

reach
"A CCK‐8 assay was performed to prove that overexpression of OTUD1 significantly suppressed cell growth (p < 0.01, Figure 2b)."

reach
"Moreover, we observed that OTUD1 overexpression induced p53-dependent apoptosis and dramatically inhibited cell growth."

reach
"In this process, OTUD1 could remove the K63 linkage ubiquitination of YAP and negatively regulate transcriptional activity and cell growth."

reach
"As expected, OTUD1 oe suppressed myeloma cell growth while introduction of sh OTUD1 promoted proliferation (Fig. 2f, g)."
OTUD1 affects SEC23B
1 | 1 3
OTUD1 binds SEC23B.
1 | 3
1 | 3

sparser
"Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII)."

No evidence text available

sparser
"Our study thus explored the role of OTUD1 in moderating periodontitis by inhibiting neutrophil secretion, suggesting that the OTUD1SEC23B axis can be a potential target for the treatment of neutrophil‐related inflammatory diseases."

sparser
"Interaction between OTUD1 and COPII subunits was confirmed by co‐immunoprecipitation assay, and OTUD1 associated strongly with SEC23B (Figure  xref )."
OTUD1 deubiquitinates SEC23B.
| 1
OTUD1 leads to the deubiquitination of SEC23B. 1 / 1
| 1

reach
"Mechanistically, OTUD1 suppressed the process of protein endoplasmic reticulum‐to‐Golgi trafficking by removing k63‐linked ubiquitination of Sec23 homologue B (SEC23B), a coat protein II complex component."
| 5
| 5

reach
"OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes."

reach
"These evidence highlighted the OTUD1‐CARD9 axis in ISO‐driven HF and suggested that targeting OTUD1 or CARD9 could have therapeutic potential for this condition."

reach
"The first study demonstrated that OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes."

reach
"In addition, OTUD1 and USP15 appear to modulate cardiac myocyte remodeling in the context of heart failure, the former by targeting STAT3 [137,138]."

reach
"First, OTUD1 upregulation in human heart failure samples was detected from public single-cell sequencing data rather than clinically acquired data."
OTUD1 affects FlaG
| 5
| 5

sparser
"Indeed, peptides derived from AIFM1, CUL3, and PGAM5 were identified in FLAG-OTUD1 co-precipitates (Fig. xref , Supplementary Fig. xref )."

sparser
"For the SEC23B half‐life assay, HEK293T cells were transfected with FLAGOTUD1 and treated with the protein synthesis inhibitor cycloheximide (Biorbyt, 100 µg mL −1 ) for the indicated time durations before collection."

sparser
"Although the co-precipitation of endogenous AIFM1 with FLAG-OTUD1 was detected by the MS analysis (Fig. xref , Supplementary Fig. xref ), the co-precipitation of exogenous OTUD1 with AIFM1 was not detected (Supplementary Fig. xref )."

sparser
"HL‐60 cells stably expressing Mock or OTUD1FLAG were treated with ATRA (1 µM) to induce differentiation of leukemic cells into granulocytes for 5 days and then stimulated by LPS (100 ng ml −1 ) for 4 h."

sparser
"To further examine the physiological roles of OTUD1, proteins interacting with FLAG-OTUD1 in HEK293T cells were analyzed by immunoprecipitation-mass spectrometry."
OTUD1 affects BCL2L11
1 | 3 1
OTUD1 activates BCL2L11.
| 3
OTUD1 activates BCL2L11. 3 / 3
| 3

reach
"Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation."

reach
"In addition, melatonin-induced activation of Sp1 was found to be involved in OTUD1 upregulation at the transcriptional level, and pharmacological inhibition and genetic ablation of Sp1 (siRNA) interrupted melatonin-induced OTUD1-mediated Bim upregulation."

reach
"Melatonin promotes the OTUD1-mediated stabilization of Bim by the deubiquitination of K3 (Figure 5A)."
OTUD1 binds BCL2L11.
1 | 1
1 | 1

sparser
"OTUD1 directly interacted with Bim and inhibited its ubiquitination."

No evidence text available
FlaG affects OTUD1
| 5
| 5

sparser
"Indeed, peptides derived from AIFM1, CUL3, and PGAM5 were identified in FLAG-OTUD1 co-precipitates (Fig. xref , Supplementary Fig. xref )."

sparser
"For the SEC23B half‐life assay, HEK293T cells were transfected with FLAGOTUD1 and treated with the protein synthesis inhibitor cycloheximide (Biorbyt, 100 µg mL −1 ) for the indicated time durations before collection."

sparser
"Although the co-precipitation of endogenous AIFM1 with FLAG-OTUD1 was detected by the MS analysis (Fig. xref , Supplementary Fig. xref ), the co-precipitation of exogenous OTUD1 with AIFM1 was not detected (Supplementary Fig. xref )."

sparser
"HL‐60 cells stably expressing Mock or OTUD1FLAG were treated with ATRA (1 µM) to induce differentiation of leukemic cells into granulocytes for 5 days and then stimulated by LPS (100 ng ml −1 ) for 4 h."

sparser
"To further examine the physiological roles of OTUD1, proteins interacting with FLAG-OTUD1 in HEK293T cells were analyzed by immunoprecipitation-mass spectrometry."
YTHDF1 affects OTUD1
| 4
YTHDF1 decreases the amount of OTUD1.
| 2
YTHDF1 decreases the amount of OTUD1. 2 / 2
| 2

reach
"Hence, we reported that the m6A-modified mRNA of OTUD1 by METTL3 was a target of YTHDF1.Next, we transfected the METTL3 plasmid and si-YTHDF1 in AC16 at the same time and demonstrated that the elevated protein expression of OTUD1 by METTL3 overexpression could be rescued by YTHDF1 silencing (Figure 3N)."

reach
"YTHDF1 overexpression could restore the decreased protein expression of OTUD1 caused by silencing METTL3 (Figure S4L)."
YTHDF1 increases the amount of OTUD1.
| 1
YTHDF1 increases the amount of OTUD1. 1 / 1
| 1

reach
"In contrast, YTHDF1 overexpression increased OTUD1 protein levels (Figure S4H) and the mRNA half-life of OTUD1 (Figure S4I)."
YTHDF1 activates OTUD1.
| 1
YTHDF1 activates OTUD1. 1 / 1
| 1

reach
"In contrast, YTHDF1 overexpression increased OTUD1 protein levels (Figure S4H) and the mRNA half-life of OTUD1 (Figure S4I)."
TYK2 affects OTUD1
| 2 2
| 2 2

reach
"Consistently, the spleen tissues of depression model mice displayed lower AHI1 levels and less interaction between OTUD1 and Tyk2 than those of normal mice (Fig. 4h)."

reach
"We noticed that AHI1 did not strongly affect OTUD1 protein levels (Fig. 4f) but affected the interaction between OTUD1 and Tyk2, as shown by the abolishment of the OTUD1-Tyk2 interaction upon AHI1 knockout in primary macrophages (Fig. 4g)."

sparser
"We noticed that AHI1 did not strongly affect OTUD1 protein levels (Fig.  xref ) but affected the interaction between OTUD1 and Tyk2, as shown by the abolishment of the OTUD1-Tyk2 interaction upon AHI1 knockout in primary macrophages (Fig.  xref )."

sparser
"Consistently, the spleen tissues of depression model mice displayed lower AHI1 levels and less interaction between OTUD1 and Tyk2 than those of normal mice (Fig.  xref )."
TRAF6 affects OTUD1
| 1 3
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
| 1

reach
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
TRAF3 affects OTUD1
| 1 3
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
| 1

reach
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
SEC23B affects OTUD1
1 | 3
1 | 3

sparser
"Mechanistically, OTUD1 interacts with SEC23B, a component of the coat protein II complex (COPII)."

No evidence text available

sparser
"Our study thus explored the role of OTUD1 in moderating periodontitis by inhibiting neutrophil secretion, suggesting that the OTUD1SEC23B axis can be a potential target for the treatment of neutrophil‐related inflammatory diseases."

sparser
"Interaction between OTUD1 and COPII subunits was confirmed by co‐immunoprecipitation assay, and OTUD1 associated strongly with SEC23B (Figure  xref )."

reach
"OTUD1 also suppresses TNF-α-induced apoptosis and necroptosis."

reach
"In this study, we showed that the genetic deficiency of OTUD1 accelerated the TNF-α-induced apoptosis and necroptosis, and the basal K63 ubiquitination of RIP3 was enhanced in Otud1 -MEFs (Figs."

reach
"OTUD1 negatively regulates the canonical NF-kappaB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway."

reach
"OTUD1 suppresses TNF-alpha-induced apoptosis and necroptosis."

reach
"A previous study showed that OTUD1 enhances iron transport and potentiates host antitumor immunity in colon cancer ."

reach
"In the intestinal lamina propria, the deletion of OTUD1 will result in significantly increased numbers of DCs during dextran sulfate sodium treatment.32 Previous research has revealed that OTUD1 can promote iron transport ferroptosis via stabilizing IREB2 and thereby induce ferroptosis."

reach
"For example, OTUD1 has been shown to enhances iron transport and potentiate antitumor immunity in colon cancer by targeting/regulating iron-responsive element-binding protein 2 33."

reach
"OTUD1 promotes transferrin receptor protein 1 (TFRC)-mediated iron transport through deubiquitination and stabilization of IREB2, leading to increased ROS production and ferroptosis."

reach
"OTUD1 causes suppression of TGF-beta downstream signals and EMT."

reach
"Combined, the in vitro and in vivo evidence in this study elucidates critical functions of OTUD1 in the termination of TGF-beta and SMAD-induced metastatic activation, indicating that OTUD1 restricts the EMT and cancer stem cell traits during metastasis."

eidos
"Moreover , OTUD1 suppresses TGF-beta signaling and EMT in MCF10A cells expressing RAS and metastasis of breast cancer cells in mice , respectively , presumably through deubiquitylating SMAD7 thus enabling SMURF2 binding and subsequent TGFR turnover43 ."

reach
"From our screen, we have identified that loss of OTUD1 enables breast cancer cells to undergo EMT and gain cancer stem cell traits thereby driving metastatic spread to distant organs, such as bone and lung."
| 2

reach
"In addition, OTUD1 reduced interferon production induced by RIG-I-like receptors [17]."

reach
"OTUD1 deficiency impaired CARD9 mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation."
| 2

reach
"Therefore, Otud1 deficiency impairs cytokine production and antifungal immune responses in vivo."

reach
"OTUD1 levels are positively correlated with the incidence and severity of aGVHD, and, therefore, Otud1 deficiency suppresses T cell activation and proinflammatory cytokine production, resulting in the alleviation of aGVHD pathogenicity."
OTUD1 affects Neoplasms
| 4
OTUD1 inhibits Neoplasms.
| 3
| 3

reach
"Therefore, the OTUD1–PTEN axis suppresses tumor growth and regulates the resistance of ccRCC to tyrosine kinase inhibitors."

reach
"Another study identified that the deubiquitinase OTUD1 suppressed tumor progression by stabilizing KLF4 in NSCLC cells [148] ."

reach
"Relatively, OTUD1 also can inhibit tumor metastasis by preventing the degradation of SMAD family member 7 (SMDA7), which can inhibit tumor metastasis by blocking TGF-β signaling pathway (Zhang et al., 2017)."
OTUD1 activates Neoplasms.
| 1
| 1

reach
"OTUD1 inhibits breast cancer metastasis by reducing TGF-β-induced tumor-promoting responses by deubiquitinating SMAD7 [7]."
OTUD1 affects NSCLC
| 4
OTUD1 inhibits NSCLC. 4 / 4
| 4

reach
"Overexpression of OTUD1 inhibited NSCLC cell progression and it was promoted by knockdown of OTUD1."

reach
"OTUD1 knockdown promotes NSCLC cell proliferation, migration and invasion."

reach
"Our study revealed that OTUD1 suppresses NSCLC progression by mediating KLF4 stabilization, which suggests a potential gene target for the future treatment of NSCLC."

reach
"Moreover, more studies need to be performed to determine whether OTUD1 exerts consistent roles in mice models.In conclusion, this investigation for the first time has elucidated that OTUD1 inhibits NSCLC cell progression including cell growth, migration and invasion by stabilizing and ubiqutinating the tumor suppressor, KLF4."
OTUD1 affects NFkappaB
| 3 1
OTUD1 activates NFkappaB.
| 2
| 2

reach
"OTUD1 is transcriptionally upregulated by the TAM/NF-kappaB signaling pathway."

reach
"OTUD1 may mediate the occurrence of stroke by activating the NF-kappaB signaling pathway in herpes simplex virus latent infection."
OTUD1 inhibits NFkappaB.
| 1
| 1

reach
"OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs."
OTUD1 binds NFkappaB.
| 1

sparser
"Studies have shown that OTUD1 interacts with NF-κB and interferes with the inflammatory response involved in NF-κB, thereby affecting the homeostatic environment in brain cells."
OTUD1 affects Ig
| 4
OTUD1 activates Ig.
| 3
OTUD1 activates Ig. 3 / 3
| 3

reach
"Moreover, a vast majority of OTUD1-associated proteins in our proteomic analysis belonged to ribosome or translation machinery (Supplementary Data 2) suggesting OTUD1 could mediate translation of Ig mRNA."

reach
"To unveil the mechanism of how OTUD1 potentiates Ig production, we performed a proximity labeling assay in cells with dox-inducible expression of OTUD1 fused to the newest generation of the biotin ligase BirA (TurboID) (Supplementary Fig. 4a)."

reach
"OTUD1 mediates Ig production and PI sensitivity through PRDX4."
OTUD1 ubiquitinates Ig.
| 1
OTUD1 leads to the ubiquitination of Ig. 1 / 1
| 1

reach
"Together, these data suggest that OTUD1 modulates MM sensitivity to PIs by regulating a load of misfolded/ubiquitinated Ig on proteasome."
OTUD1 affects ISO
| 4
OTUD1 activates ISO. 4 / 4
| 4

reach
"These findings provided evidence that myeloid OTUD1 mediated ISO‐induced CARD9‐BCL10 interaction, cardiac inflammation, hypertrophy and dysfunction in mice.4 DISCUSSION."

reach
"In summary, we have demonstrated that the macrophage OTUD1‐CARD9 axis mediates ISO‐induced inflammatory response, subsequently contributing to heart remodelling."

reach
"Macrophage OTUD1 mediates ISO‐driven inflammatory responses by deubiquitinating CARD9 and increasing the combination of CARD9 and BCL10.The cellular mechanism linking CARD9 to CLRs, specifically through the Dectin‐1 signalling pathway, has been well‐documented in the context of fungal and parasitic infections."

reach
"Noninvasive echocardiography showed that OTUD1 deficiency significantly inhibited ISO‐induced cardiac dysfunction (Table 3 and Figure S13A)."
OTUD1 affects IFNB1
| 4
OTUD1 inhibits IFNB1.
| 3
OTUD1 inhibits IFNB1. 3 / 3
| 3

reach
"Our data showed that overexpression of OTUD1 inhibited the production of IFNbeta in response to SeV infection, whereas knockdown of Smurf1 largely blocked the negative regulation of OTUD1 on IFNbeta production (XREF_FIG), indicating that Smurf1 is required for OTUD1 mediated inhibition of interferon antiviral response."

reach
"The result showed that knockdown of OTUD1 promoted SeV induced IFNbeta production (XREF_FIG and XREF_SUPPLEMENTARY)."

reach
"During infection with SeV, overexpression of OTUD1-wild type obviously lowered the activity of IFNbeta promoter, whereas overexpression of OTUD1-CH mutant completely had no effect on the IFNbeta promoter activity (XREF_FIG), suggesting that the deubiquitinase activity of OTUD1 is important for OTUD1 mediated inhibition of IFNbeta production during viral infection."
OTUD1 activates IFNB1.
| 1
OTUD1 activates IFNB1. 1 / 1
| 1

reach
"At day 3 after VSV infection, Otud1 -/- mice produced much higher expression of IFNbeta and IL-6 mRNAs (XREF_FIG), and had much lower viral RNAs (XREF_FIG) in their lung tissue than did Otud1 +/+ mice."
OTUD1 affects FLNC
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
OTUD1 affects EGFP
| 4
| 4

sparser
"An EGFP-OTUD1 inducible system was then constructed to evaluate the effect of OTUD1 on JNK pathway proteins."

sparser
"An EGFP-OTUD1 inducible plasmid was then constructed to evaluate the dynamics of the colocalization of OTUD1 and ASK1."

sparser
"As shown in Fig.  xref and Supplementary Fig.  xref , live 293T cells transiently transfected with EGFP-OTUD1 WT were subjected to laser microirradiation."

sparser
"An EGFP-OTUD1 inducible system was again used to evaluate the dynamics of the colocalization of OTUD1 and ASK1."
OTUD1 affects DCAF10
3 | 1
3 | 1

No evidence text available

No evidence text available

No evidence text available

sparser
"The results showed that only DCAF10 associated with OTUD1 in vitro (Figure S7A–C, Supporting Information)."
| 4

reach
"OTUD1 upregulation suppressed cell viability and invasion and migration via mediating stabilization of KLF4, while silencing of OTUD1 showed the opposite effect [148] ."

reach
"A CCK‐8 assay was employed to illustrate that overexpression of KLF4 effectively reduced cell viability increased by knockdown of OTUD1 (p < 0.01, Figure 6b)."

reach
"Depletion of endogenous OTUD1 potentiated the capacity of RAS transformed MCF10A cells to form tumor organoids in 3D Matrigel but did not inhibit tumor cell survival and proliferation under standard 2D culture conditions."

reach
"CCK‐8 assay showed that OTUD1 knockdown dramatically upregulated the cell viability of PC9 and A549 cells (p < 0.01, Figure 3b)."
OTUD1 affects CEBPB
| 2 2
OTUD1 binds CEBPB.
| 1 2
| 1 2

reach
"Mechanistically, OTUD1 bound to C/EBPβ and maintained its stability by removing the K48 ubiquitin chain at K253 of C/EBPβ, thereby activating the C/EBPβ-nuclear factor-κB-mediated inflammatory responses in microglia."

sparser
"Mechanistically, OTUD1 bound to C/EBPβ and maintained its stability by removing the K48 ubiquitin chain at K253 of C/EBPβ, thereby activating the C/EBPβ-nuclear factor-κB-mediated inflammatory responses in microglia."

sparser
"Overall, our results revealed the roles of the OTUD1-C/EBPβ axis in mediating the microglial inflammatory responses and AD pathology, facilitating the development of new strategies targeting microglial neuroinflammation for AD treatment."
OTUD1 deubiquitinates CEBPB.
| 1
OTUD1 deubiquitinates CEBPB. 1 / 1
| 1

reach
"OTUD1 positively regulates microglia neuroinflammation and promotes the pathogenesis of Alzheimer's disease by deubiquitinating C/EBPβ."
OTUD1 affects CDK9
| 3 1
OTUD1 binds CDK9.
| 1 1
| 1 1

sparser
"In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells."

reach
"In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells."
OTUD1 deubiquitinates CDK9.
| 1
OTUD1 deubiquitinates CDK9. 1 / 1
| 1

reach
"OTUD1 promotes hypertensive kidney fibrosis and injury by deubiquitinating CDK9 in renal epithelial cells."
OTUD1 activates CDK9.
| 1
OTUD1 activates CDK9. 1 / 1
| 1

reach
"This study demonstrates that OTUD1 mediates HRD by targeting CDK9 in kidney epithelial cells, suggesting OTUD1 is a potential target in treating this disease."
OTUD1 affects AP1G1
| 2 2
OTUD1 binds AP1G1.
| 1 2
| 1 2

sparser
"The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays."

sparser
"Among these proteins, we verified that OTUD1 could interact with AP1G1, which was ubiquitinated in goose liver, and the protein level of AP1G1 was significantly higher than that of normal liver without increase of mRNA level of AP1G1 in goose fatty liver."

reach
"The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays."
OTUD1 inhibits AP1G1.
| 1
OTUD1 inhibits AP1G1. 1 / 1
| 1

reach
"It suggests that the elevated protein level of OTUD1 in goose fatty liver may increase the protein level of AP1G1 in goose fatty liver by deubiquitinating AP1G1 protein and inhibiting the decrease of AP1G1 protein."
KLF4 affects OTUD1
| 3 1
KLF4 inhibits OTUD1.
| 2
KLF4 inhibits OTUD1. 2 / 2
| 2

reach
"The rescue experiments revealed that overexpression of KLF4 eliminated the function of OTUD1 in NSCLC cells, suggesting that OTUD1 suppressed NSCLC progression via targeting KLF4 [148] ."

reach
"Overexpressing KLF4 dramatically eliminated the effects of OTUD1 on the development of NSCLC cells."
KLF4 binds OTUD1.
| 1
| 1

sparser
"For example, we did not verify whether OTUD1 interacts with KLF4 directly and confirm the ubiquitination site of KLF4."
KLF4 activates OTUD1.
| 1
KLF4 activates OTUD1. 1 / 1
| 1

reach
"Furthermore, overexpression of KLF4 effectively eliminated the effect of OTUD1 knockdown on NSCLC cell progression as expected.OTUD1 as a type of cysteine protease containing OTU domain is capable of hydrolyzing the cleavage of polyubiquitin chains."
FLNC affects OTUD1
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
EGFP affects OTUD1
| 4
| 4

sparser
"An EGFP-OTUD1 inducible system was then constructed to evaluate the effect of OTUD1 on JNK pathway proteins."

sparser
"An EGFP-OTUD1 inducible plasmid was then constructed to evaluate the dynamics of the colocalization of OTUD1 and ASK1."

sparser
"As shown in Fig.  xref and Supplementary Fig.  xref , live 293T cells transiently transfected with EGFP-OTUD1 WT were subjected to laser microirradiation."

sparser
"An EGFP-OTUD1 inducible system was again used to evaluate the dynamics of the colocalization of OTUD1 and ASK1."
DCAF10 affects OTUD1
3 | 1
3 | 1

No evidence text available

No evidence text available

No evidence text available

sparser
"The results showed that only DCAF10 associated with OTUD1 in vitro (Figure S7A–C, Supporting Information)."
Paracetamol affects OTUD1
3 |
Paracetamol increases the amount of OTUD1. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
1 | 2
Hexadecanoic acid increases the amount of OTUD1.
| 2
Hexadecanoic acid increases the amount of OTUD1. 2 / 2
| 2

reach
"High concentrations of palmitic acid and oleic acid could induce the expression of OTUD1 in goose primary hepatocytes."

reach
"In goose primary hepatocytes, palmitic acid and oleic acid both increased the protein levels of OTUD1, while glucose and insulin inhibited the expression of the protein."
Hexadecanoic acid decreases the amount of OTUD1.
1 |
Hexadecanoic acid decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
TRAF6 affects TRAF3
| 3
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
SP1 affects OTUD1
| 3
SP1 activates OTUD1. 3 / 3
| 3

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"Thus, our results demonstrated that melatonin induced apoptosis by stabilizing Bim via Sp1-mediated OTUD1 upregulation."

reach
"Furthermore, melatonin upregulates Sp1 expression, which directly activates the OTUD1 promoter."

reach
"Melatonin induces apoptotic cell death through Bim stabilization by Sp1-mediated OTUD1 upregulation."
OTUD1 affects cell death
| 3
| 3

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"The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein."

reach
"The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein."

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"These results indicated that OTUD1 suppresses the NF-κB-mediated inflammatory and ROS-induced oxidative damage responses, as well as cell death through specific deubiquitination in an in vivo colitis model.To further clarify the pathophysiological role of OTUD1 in vivo, we adopted LPS/GalN-induced acute hepatitis and LPS-induced sepsis models, which are associated with inflammatory and oxidative responses [29–31]."

reach
"OTUD1 deletion attenuates vascular remodeling, collagen deposition, and endothelial-to-mesenchymal transition."

reach
"Finally, SMAD3 inhibition reverses OTUD1-promoted vascular remodeling."

reach
"We detect upregulated OTUD1 in the vascular endothelium of Ang II-challenged mice and show that OTUD1 deletion attenuates vascular remodeling, collagen deposition, and EndMT."
OTUD1 affects RLR
| 3
OTUD1 inhibits RLR. 3 / 3
| 3

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"Finally, the deubiquitinase OTUD1 potently inhibits RLR pathway by utilizing Smurf1-MAVS/TRAF3/TRAF6 signaling at the early stage of viral infection."

reach
"OTUD1 then removes the K63-linked ubiquitin chain from K98 of IRF3 and attenuates the RIG-I-like receptors (RLRs)-mediated IFN production pathway (Figure 4A)."

reach
"Our study clearly demonstrates that the deubiquitinase OTUD1 negatively regulates RLR signaling."
OTUD1 affects JNK
| 3
OTUD1 activates JNK. 3 / 3
| 3

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"Mechanistically, leptin treatment significantly increased the chromatin enrichment of the transcription factor c-Jun, including the OTUD1 gene enhancer, which was sufficient to increase the OTUD1 protein level and subsequently cause OTUD1 aggresome formation, ASK1 recruitment and JNK/c-Jun pathway activation."

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"OTUD1 activates the ASK1-p38/JNK pathways during cardiac hypertrophy."

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"These results demonstrate that OTUD1 activates the ASK1-p38/JNK signaling pathway in response to pro-hypertrophy stimulation."
OTUD1 affects IFNbeta promoter
| 3
OTUD1 inhibits IFNbeta promoter. 3 / 3
| 3

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"Results showed that knockdown of OTUD1 significantly enhanced activation of IFNbeta promoter during SeV infection (XREF_SUPPLEMENTARY), and overexpression of OTUD1 inhibited SeV induced activation of IFNbeta promoter (XREF_SUPPLEMENTARY)."

reach
"To further determine at what level in RLRs mediated antiviral signaling pathway OTUD1 blocked activation of IFNbeta promoter, three expression constructs (RIG-I, MAVS, or TBK1) were overexpressed in cells in the presence or absence of OTUD1."

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"The results showed that OTUD1 overexpression dramatically inhibited IFNbeta promoter activation driven by both RIG-I and MAVS (XREF_FIG), whereas IFNbeta promoter activation by TBK1 (XREF_FIG) was not inhibited by OTUD1 coexpression."
OTUD1 affects GST
| 3
| 3

sparser
"Moreover, recombinant GST-OTUD1 completely hydrolyzed the K63-linked polyubiquitin chain, and processed a long K48-linked polyubiquitin chain to tetraubiquitin (Supplementary Fig. xref )."

sparser
"To ensure that OTUD1 interacts directly with Akt, we further constructed and purified GST-OTUD1 and His-Akt from E . coli ( Figure S1 C), and pulldown assays were performed."

sparser
"An in vitro pulldown assay with purified GST-OTUD1 and His-PH demonstrated that the Akt PH domain directly bound to OTUD1 ( Figures 3 D and S3 C)."
OTUD1 affects FLNB
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OTUD1 affects FLNA
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OTUD1 affects FHL1
3 |
3 |

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| 3
OTUD1 inhibits Cell Hypoxia.
| 2
| 2

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"In addition, Nrf2 deletion impaired Otud1 ability in reducing pro-apoptotic proteins and elevating anti-apoptotic protein Bcl2 in H/R-stimulated primary hepatocytes (Fig. S7A)."

reach
"These findings indicate that OTUD1 attenuates mitochondria damage caused by oxidative stress following H/R treatment in vitro.2.4 OTUD1 mitigates hepatocyte H/R injury by activating NRF2/ARE pathway."
OTUD1 activates Cell Hypoxia.
| 1
| 1

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"Next, we investigated the specific signaling pathway activated by OTUD1 in hepatocytes under H/R exposure."
OTUD1 affects CTNNB1
1 | 2
1 | 2

sparser
"Mechanistically, OTUD1 directly interacted with β-catenin, reducing its K63-linked ubiquitination at residues K496, K508, and K625 via its catalytic site C320."

sparser
"These findings elucidate the OTUD1-β-catenin pathway's role in endothelial dysfunction-associated angiogenesis and suggest OTUD1 as a promising therapeutic target for diabetic non-healing wounds."

No evidence text available
OTUD1 affects CDKN1A
| 3
OTUD1 increases the amount of CDKN1A. 2 / 2
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"OTUD1 also upregulates the expression of p21 and Mdm2, thus accelerating apoptosis [35], and cleaves K33-linked polyubiquitin chains from the TGF-β pathway inhibitor SMAD7 [15]."

reach
"OTUD1 also upregulates the expression of p21 and Mdm2, thus accelerating apoptosis (Piao et al., 2017)."
OTUD1-C320S increases the amount of CDKN1A. 1 / 1
| 1

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"Furthermore, the C320S OTUD1 mutant did not increase p21 and Mdm2 expression unlike WT OTUD1."
OTUD1 affects Aurora-A
| 3
OTUD1 deubiquitinates Aurora-A.
| 2
OTUD1 deubiquitinates Aurora-A. 2 / 2
| 2

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"Only OTUD1 and OTUD6A induced the deubiquitination of Aurora-A (XREF_FIG a)."

reach
"OTUD1, one of the final candidate DUBs for Aurora-A, bound to and deubiquitinated Aurora-A but its interaction with endogenous Aurora-A was much weaker than OTUD6A."
OTUD1 binds Aurora-A.
| 1
OTUD1 binds Aurora-A. 1 / 1
| 1

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"OTUD1, one of the final candidate DUBs for Aurora-A, bound to and deubiquitinated Aurora-A but its interaction with endogenous Aurora-A was much weaker than OTUD6A."
MAVS affects OTUD1
| 1 2
| 1 1

sparser
"Our data showed that OTUD1 was able to interact with MAVS ( xref )."

reach
"To further identify the signaling proteins targeted by OTUD1, the interaction between OTUD1 and MAVS was first analyzed."
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
Infections affects OTUD1
| 3
Infections increases the amount of OTUD1. 3 / 3
| 3

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"In addition, Sendai virus (SeV) infection promotes the deubiquitinase OTUD1 expression followed by upregulating protein levels of Smurf1 to degrade MAVS, and Smurf1 proteins interact with the MAVS/TRAF3/TRAF6 signalosome in cells infected with SeV for 8 h (48)."

reach
"Indeed, it was shown that infection with RNA viruses stimulates the expression of the enzyme OTU deubiquitinase1 (OTUD1), which interacts with Smurf1 and increases its intracellular expression in HEK293 lineage cells (83)."

reach
"In a somewhat controversial report, Zhang et al. show that OTUD1 expression is upregulated by both SeV and HSV infections, and Otud1-deficiency enhances the antiviral innate immune response and exhibits resistance against SeV and HSV infection [38]."
GST affects OTUD1
| 3
| 3

sparser
"Moreover, recombinant GST-OTUD1 completely hydrolyzed the K63-linked polyubiquitin chain, and processed a long K48-linked polyubiquitin chain to tetraubiquitin (Supplementary Fig. xref )."

sparser
"To ensure that OTUD1 interacts directly with Akt, we further constructed and purified GST-OTUD1 and His-Akt from E . coli ( Figure S1 C), and pulldown assays were performed."

sparser
"An in vitro pulldown assay with purified GST-OTUD1 and His-PH demonstrated that the Akt PH domain directly bound to OTUD1 ( Figures 3 D and S3 C)."
FLNB affects OTUD1
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FLNA affects OTUD1
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FHL1 affects OTUD1
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CTNNB1 affects OTUD1
1 | 2
1 | 2

sparser
"Mechanistically, OTUD1 directly interacted with β-catenin, reducing its K63-linked ubiquitination at residues K496, K508, and K625 via its catalytic site C320."

sparser
"These findings elucidate the OTUD1-β-catenin pathway's role in endothelial dysfunction-associated angiogenesis and suggest OTUD1 as a promising therapeutic target for diabetic non-healing wounds."

No evidence text available
CEBPB affects OTUD1
| 1 2
| 1 2

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"Mechanistically, OTUD1 bound to C/EBPβ and maintained its stability by removing the K48 ubiquitin chain at K253 of C/EBPβ, thereby activating the C/EBPβ-nuclear factor-κB-mediated inflammatory responses in microglia."

sparser
"Mechanistically, OTUD1 bound to C/EBPβ and maintained its stability by removing the K48 ubiquitin chain at K253 of C/EBPβ, thereby activating the C/EBPβ-nuclear factor-κB-mediated inflammatory responses in microglia."

sparser
"Overall, our results revealed the roles of the OTUD1-C/EBPβ axis in mediating the microglial inflammatory responses and AD pathology, facilitating the development of new strategies targeting microglial neuroinflammation for AD treatment."
AP1G1 affects OTUD1
| 1 2
| 1 2

sparser
"The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays."

sparser
"Among these proteins, we verified that OTUD1 could interact with AP1G1, which was ubiquitinated in goose liver, and the protein level of AP1G1 was significantly higher than that of normal liver without increase of mRNA level of AP1G1 in goose fatty liver."

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"The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays."
Tetrachloromethane increases the amount of OTUD1. 2 / 2
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Polyubiquitin chains affects OTUD1
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OTUD1 binds polyubiquitin chains. 2 / 2
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"We also found that the deubiquitinase OTUD1 directly interacts with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathways."

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"OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-kappaB and MAPK pathway."
Phenylmercury acetate decreases the amount of OTUD1. 2 / 2
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Oleic acid affects OTUD1
| 2
Oleic acid increases the amount of OTUD1. 2 / 2
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"High concentrations of palmitic acid and oleic acid could induce the expression of OTUD1 in goose primary hepatocytes."

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"In goose primary hepatocytes, palmitic acid and oleic acid both increased the protein levels of OTUD1, while glucose and insulin inhibited the expression of the protein."
MiR-26a affects OTUD1
| 2
MiR-26a inhibits OTUD1.
| 1
MiR-26a inhibits OTUD1. 1 / 1
| 1

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"Therefore, we believed that miR-26a inhibited EphA2 more significantly comparing with Otud1."
MiR-26a decreases the amount of OTUD1.
| 1
MiR-26a decreases the amount of OTUD1. 1 / 1
| 1

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"The results showed that miR-26a also inhibited the expression of Otud1 (Fig. S3)."
Melatonin affects OTUD1
| 2
| 2

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"Melatonin-induced OTUD1 upregulation caused deubiquitnation at the lysine 3 residue of Bim, resulting in its stabilization."

reach
"Furthermore, melatonin reduced tumor growth and induced upregulation of OTUD1 and Bim in a mouse xenograft model."
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Hsa-miR-19b-3p decreases the amount of OTUD1. 2 / 2
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Hsa-miR-181a-5p decreases the amount of OTUD1. 2 / 2
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Cyclosporin A increases the amount of OTUD1. 2 / 2
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Benzo[a]pyrene demethylates OTUD1.
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Benzo[a]pyrene decreases the amount of OTUD1.
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Benzo[a]pyrene decreases the amount of OTUD1. 1 / 1
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UBC affects OTUD1
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RAD23B affects OTUD1
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RACK1 affects OTUD1
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reach
"In this process, OTUD1 preferentially removes the K48-linked ubiquitin chain over the K63 chain, and the OTUD1-mediated cell cycle arrest then leads to apoptosis (Figure 2A)."

reach
"Moreover, more studies need to be performed to determine whether OTUD1 exerts consistent roles in mice models.In conclusion, this investigation for the first time has elucidated that OTUD1 inhibits NSCLC cell progression including cell growth, migration and invasion by stabilizing and ubiqutinating the tumor suppressor, KLF4."

reach
"OTUD1 mediates Ig production and PI sensitivity through PRDX4."

reach
"OTUD1 modulates IgL production, proteasome load and PI sensitivity."
OTUD1 affects production
| 2
OTUD1 inhibits production. 2 / 2
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sparser
"In a screen of deubiquitinases expression cloning library [ xref , xref ], we found that the deubiquitinase OTUD1 could inhibit RNA virus-induced production of type I IFNs."

sparser
"As a consequence, OTUD1 inhibits MAVS/TRAF3/TRAF6 signalosome-mediated production of type I IFNs and proinflammatory cytokines during RNA virus infection ( xref )."

reach
"OTUD1 down-regulates inflammatory cytokine-induced canonical NF-kappaB activation."

reach
"OTUD1 negatively regulates the canonical NF-kappaB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway."
OTUD1 affects polyubiquitin chains
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OTUD1 binds polyubiquitin chains. 2 / 2
| 2

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"We also found that the deubiquitinase OTUD1 directly interacts with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathways."

reach
"OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-kappaB and MAPK pathway."
OTUD1 affects pathway
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OTUD1 activates pathway. 2 / 2
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sparser
"To study the mechanism underlying the activation of the caspase‐independent apoptosis pathway by OTUD1, we transfected Flag‐tagged OTUD1 into 293T cells and performed an immunoprecipitation assay using anti‐Flag magnetic beads."

sparser
"These findings indicate that OTUD1 stabilizes and activates NRF2/ARE pathway in hepatocytes."
OTUD1 affects nicD
| 2
OTUD1 activates nicD. 2 / 2
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"Activation of CD4+ T cells after allo-HSCT elevated the protein levels of OTUD1, which in turn interacted with the Notch2-ICD (NICD) to cleave the ubiquitin of NICD at the K1770 site, thereby inducing NICD protein accumulations in T cells."

reach
"OTUD1-driven NICD signaling promoted the differentiation and functions of Th1 and Th17 cells and amplified the cascade of aGVHD."
OTUD1 affects ferroptosis
| 2
| 2

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"In the intestinal lamina propria, the deletion of OTUD1 will result in significantly increased numbers of DCs during dextran sulfate sodium treatment.32 Previous research has revealed that OTUD1 can promote iron transport ferroptosis via stabilizing IREB2 and thereby induce ferroptosis."

reach
"Therefore, high expression of OTUD1 promotes ferroptosis in colon cancer cells via the OTUD1-IREB2-TFR1 signaling axis, while also enhancing the cytotoxic effects of T cells."
OTUD1 affects cell cycle
| 2
| 2

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"OTUD1 negatively regulates the cell cycle to inhibit the abnormal proliferation of cancer cells, since OTUD1 interacts with phosphatase and tensin homolog (PTEN), a negative regulator of the AKT (also known as protein kinase B) and NF-κB signaling pathways, and regulates its stability (Figure 2C)."

reach
"These results suggest that OTUD1 inhibits cell proliferation by regulating cell cycle and apoptosis.p53 is a master transcription factor that performs critical regulatory functions in cells."
OTUD1 affects VIM
| 1 1
OTUD1 decreases the amount of VIM.
| 1
Modified OTUD1 decreases the amount of VIM. 1 / 1
| 1

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"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2, FN1, and VIM."
OTUD1 binds VIM.
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CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
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sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
OTUD1 affects Ubiquitin
| 2
| 2

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"Furthermore, quite recently OTUD1 was found to suppress IBD by removing the K63 ubiquitin chain from RIP1 [28]."

reach
"OTUD1 was found to reverse K48 ubiquitin chain in PDE5A through cysteine at position 320 of OTUD1, preventing its proteasomal degradation."
OTUD1 affects UBC
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OTUD1 affects TRAF3, and TRAF6
| 2
| 2

sparser
"Therefore, we studied whether OTUD1 could interact with TRAF3 or TRAF6."

sparser
"Results showed that OTUD1 was also capable of interacting with both TRAF3 ( xref ) and TRAF6 ( xref )."
OTUD1 affects TNF
1 | 1
OTUD1 increases the amount of TNF.
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OTUD1 increases the amount of TNF. 1 / 1
| 1

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"OTUD1 deficiency further inhibited the activation of NF‐κB, reduced Il6 and Tnf transcript levels and limited the protein release of IL6 and TNF‐α in ISO‐stimulated MPMs (Figure 6C–F and Figure S8)."
OTUD1 binds TNF.
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OTUD1 affects TFRC
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OTUD1 decreases the amount of TFRC. 2 / 2
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"OTU deubiquitinase 1 (OTUD1) acts as a deubiquitinase of iron-responsive element-binding protein 2 (IREB2) and blocks its degradation, thereby promoting CD71 expression and augmenting cellular iron up[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"143 OTUD1 promotes the deubiquitination of IREB2, which inhibits the degradation of IREB2 protein and activates the expression of TFRC, thereby increasing the concentration of iron ions in tumor cells and enhancing the sensitivity to ferroptosis as well as the infiltration of CD8+ T cells, improving antitumor immune response."
OTUD1 affects Stroke
| 2
OTUD1 activates Stroke. 2 / 2
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"OTUD1 may mediate the occurrence of stroke by activating the NF-kappaB signaling pathway in herpes simplex virus latent infection."

reach
"Therefore, we speculate that OTUD1 may mediate the occurrence of stroke in herpes simplex virus latent infection by activating the NF-κB signaling pathway."
OTUD1 affects SMURF2
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OTUD1 activates SMURF2. 2 / 2
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"Given our results that OTUD1 enables SMAD7 and SMURF2 function, we examined whether OTUD1 misexpression can regulate TbetaRI levels at the cell surface, the location where intracellular signaling is initiated."

reach
"In line with this, knockdown of OTUD1, which results in increased K33-poly-ubiquitin conjugation on SMAD7 K220, reduced the ability of SMURF2 to interact with SMAD7."
OTUD1 affects SMAD
| 2
OTUD1 inhibits SMAD. 2 / 2
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"We next investigated the molecular mechanism by which OTUD1 inhibits TGF-beta and SMAD signaling."

reach
"Relatively, OTUD1 also can inhibit tumor metastasis by preventing the degradation of SMAD family member 7 (SMDA7), which can inhibit tumor metastasis by blocking TGF-β signaling pathway (Zhang et al., 2017)."
OTUD1 affects SKP2
| 1 1
OTUD1 inhibits SKP2.
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OTUD1 inhibits SKP2. 1 / 1
| 1

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"Here, we report that YAP is subject to non proteolytic, K63 linked polyubiquitination by the SCF SKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1."
OTUD1 binds SKP2.
| 1
| 1

sparser
"To assess whether the expression of SKP2 or OTUD1 is associated with clinical outcomes in breast cancer patients, we performed Kaplan–Meier (KM) plotter analysis of microarray datasets of human mammary tumors xref ."
OTUD1 decreases the amount of Reactive Oxygen Species. 2 / 2
| 2

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"As expected, OTUD1 reduced apoptosis rate, enhanced MMP and attenuated ROS levels in AML12 under H/R conditions (Figs."

reach
"Therefore, OTUD1 may antagonize these E3s.In the presence of excess amounts of ROS, KEAP1 induces cell death named oxeiptosis through binding with PGAM5 and AIFM1 [25]."
OTUD1 affects RIGI
| 2
OTUD1 increases the amount of RIGI.
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Modified OTUD1 increases the amount of RIGI. 1 / 1
| 1

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"Our data showed that OTUD1 overexpression had no obvious effects on IRF3 and TBK1 protein levels, and increased RIG-I protein levels to some extent (XREF_FIG)."
OTUD1 deubiquitinates RIGI.
| 1
OTUD1 leads to the deubiquitination of RIGI on K48. 1 / 1
| 1

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"OTUD1 inhibits innate antiviral immunity in response to RNA and DNA viruses ( Zhang et al., 2018 , 2020b , 2020c ), OTUD4 promotes antiviral response by deubiquitinating and stabilizing MAVS ( Liuyu e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD1 affects RIG-I-like receptors
| 2
OTUD1 inhibits RIG-I-like receptors. 2 / 2
| 2

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"Under inflammatory conditions, inducible OTUD1 acts as an immune checkpoint and blocks RIG-I-like receptors signaling."

reach
"OTUD1 then removes the K63-linked ubiquitin chain from K98 of IRF3 and attenuates the RIG-I-like receptors (RLRs)-mediated IFN production pathway (Figure 4A)."
OTUD1 affects RAD23B
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OTUD1 affects RACK1
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OTUD1 affects Pathway
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OTUD1 activates Pathway. 2 / 2
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sparser
"OTUD1 Activates the Caspase‐Independent Apoptosis Pathway."

sparser
"OTUD1 Recruits the CUL4A‐DDB1 Complex to Promote MCL1 Degradation and Activate the Caspase‐Dependent Apoptosis Pathway."
OTUD1 affects PDE5A
| 2
OTUD1 deubiquitinates PDE5A. 2 / 2
| 2

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"In conclusion, OTUD1 promotes heart failure by deubiquitinating and stabilizing PDE5A in cardiomyocytes."

reach
"This study showed that OTUD1 deubiquitinates PDE5A, leading to its stabilization and increased cGMP degradation, which exacerbates cardiac hypertrophy and heart failure 58.Our research advances the understanding of OTUD1's role in cardiac hypertrophy and remodeling by elucidating the specific molecular mechanism involving the METTL3-mediated m6A modification of OTUD1 mRNA."
OTUD1 affects PCSK9
| 2
OTUD1 inhibits PCSK9. 2 / 2
| 2

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"Transwell assay demonstrated that silencing OTUD1 significantly accelerated PC9 and A549 cell migration and invasion (p < 0.01, Figure 3c,d)."

reach
"CCK‐8 assay showed that OTUD1 knockdown dramatically upregulated the cell viability of PC9 and A549 cells (p < 0.01, Figure 3b)."
OTUD1 affects OSCS
| 2
OTUD1 activates OSCS. 2 / 2
| 2

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"Taken together, these results strongly suggest that OTUD1 may act as a proto-oncogene in ovarian cancer and potentiate OSCS maintenance."

reach
"ASK1/JNK inhibitors very effectively suppressed OSCS induced by OTUD1 overexpression (Fig. 6), and ibrutinib, an FDA-approved MKK7 inhibitor, preferentially reduced the tumorigenicity of OTUD1 ovarian cancer cells (Fig. 7)."
OTUD1 affects NOTCH2
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OTUD1 affects Mice
| 2
OTUD1 inhibits Mice. 2 / 2
| 2

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"Our group has recently found that cardiomyocyte OTUD1 promoted angiotensin II‐ and TAC‐driven cardiac dysfunction, hypertrophy and fibrosis, while the role of OTUD1 was evaluated using the whole‐body OTUD1 knockout mice but not the myocardial‐specific OTUD1 knockout mice or BMT."

reach
"Additionally, OTUD1 and FGL1 depletion significantly restored TNFα-reduced anticancer immunity and prolonged the OS of mice stimulated with TNFα (Fig. 6C, D, S5D), consistent with the above in vitro findings."
OTUD1 affects MDM2
| 1
OTUD1 increases the amount of MDM2. 1 / 2
| 1

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"OTUD1 also upregulates the expression of p21 and Mdm2, thus accelerating apoptosis [35], and cleaves K33-linked polyubiquitin chains from the TGF-β pathway inhibitor SMAD7 [15]."
OTUD1 affects K48-
| 2
OTUD1 deubiquitinates K48- on K63. 2 / 2
| 2

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"Song et al. showed that OTUD1 binds IREB2 through the N-terminal APGR, and deubiquitinates K48- and K63-linked ubiquitin chains from IREB2."

reach
"Indeed, OTUD1 associates with the C-terminal MH2 domain of SMAD3 and deubiquitinates K48- and K63 ubiquitin chains from SMAD3, thus, contributing to SMAD3 activity, SMAD3/SMAD4 complex formation, and nuclear translocation (Figure 6D)."
OTUD1 affects K33
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OTUD1 binds CARD9 and K33. 2 / 2
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"32 We demonstrate that OTUD1 binds to the CARD9 and removes the K33‐linked ubiquitin from CARD9, thus promoting the assembly of the CBM complex in macrophages upon ISO stimulation."

reach
"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability."
OTUD1 affects JUN
| 2
OTUD1 phosphorylates JUN.
| 1
OTUD1 leads to the phosphorylation of JUN. 1 / 1
| 1

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"In addition, loss of OTUD1 reduced the c-Jun phosphorylation level in SKOV3, OVCAR8 and CAOV3 cells (Supplementary Fig. 2e), implying that OTUD1 probably regulates OSCS by activating the JNK/c-Jun pathway.Moreover, depletion of OTUD1 reduced the ASK1 phosphorylation level in SKOV3 and OVCAR8 cells (Supplementary Fig. 2f)."
OTUD1 dephosphorylates JUN.
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OTUD1 leads to the dephosphorylation of JUN. 1 / 1
| 1

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"In addition, loss of OTUD1 reduced the c-Jun phosphorylation level in SKOV3, OVCAR8 and CAOV3 cells (Supplementary Fig. 2e), implying that OTUD1 probably regulates OSCS by activating the JNK/c-Jun pathway.Moreover, depletion of OTUD1 reduced the ASK1 phosphorylation level in SKOV3 and OVCAR8 cells (Supplementary Fig. 2f)."
OTUD1 affects Infections
| 2
| 2

reach
"OTUD1 may mediate the occurrence of stroke by activating the NF-kappaB signaling pathway in herpes simplex virus latent infection."

reach
"Therefore, we speculate that OTUD1 may mediate the occurrence of stroke in herpes simplex virus latent infection by activating the NF-κB signaling pathway."
OTUD1 affects Collagen
| 2
| 2

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"We detect upregulated OTUD1 in the vascular endothelium of Ang II-challenged mice and show that OTUD1 deletion attenuates vascular remodeling, collagen deposition, and EndMT."

reach
"OTUD1 deletion attenuates vascular remodeling, collagen deposition, and endothelial-to-mesenchymal transition."

eidos
"Our study revealed that OTUD1 suppresses NSCLC progression by mediating KLF4 stabilization , which suggests a potential gene target for the future treatment of NSCLC ."

reach
"The deubiquitinase OTUD1 inhibits non-small cell lung cancer progression by deubiquitinating and stabilizing KLF4 ."
| 2
OTUD1 inhibits Carcinogenesis.
| 1

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"Importantly, a xenograft of MDA-MB-231 cells expressing YAP with mutated Lys residues that accept K63 ubiquitination showed attenuated tumorigenesis, whereas the knockdown of OTUD1 enhanced tumorigenesis, suggesting that OTUD1 is an important inhibitor of tumorigenesis."
OTUD1 activates Carcinogenesis.
| 1

reach
"Importantly, a xenograft of MDA-MB-231 cells expressing YAP with mutated Lys residues that accept K63 ubiquitination showed attenuated tumorigenesis, whereas the knockdown of OTUD1 enhanced tumorigenesis, suggesting that OTUD1 is an important inhibitor of tumorigenesis."
OTUD1 affects CFH
| 2
OTUD1 ubiquitinates CFH.
| 1
OTUD1 ubiquitinates CFH. 1 / 1
| 1

reach
"These results indicated that the deubiquitinase OTUD1, which was upregulated by VE-822, inhibited the progression of LUAD in vitro and in vivo by deubiquitinating and stabilizing FHL1."
OTUD1 deubiquitinates CFH.
| 1
OTUD1 deubiquitinates CFH. 1 / 1
| 1

reach
"These results indicated that the deubiquitinase OTUD1, which was upregulated by VE-822, inhibited the progression of LUAD in vitro and in vivo by deubiquitinating and stabilizing FHL1."
OTUD1 affects CDKN2A
2 |
2 |

No evidence text available

No evidence text available
OTUD1 affects CDIPT
| 2
OTUD1 activates CDIPT. 2 / 2
| 2

reach
"As expected, OTUD1 oe (high iIgL) increased the sensitivity of MM cells to all clinically used PIs, while the cells with OTUD1 knock-down (low iIgL) developed profound PI resistance (Fig. 3i, j)."

reach
"Together, these data suggest that OTUD1 modulates MM sensitivity to PIs by regulating a load of misfolded/ubiquitinated Ig on proteasome."
OTUD1 affects CDH2
| 1 1
OTUD1 decreases the amount of CDH2.
| 1
Modified OTUD1 decreases the amount of CDH2. 1 / 1
| 1

reach
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2, FN1, and VIM."
OTUD1 binds CDH2.
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
| 1

sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
OTUD1 affects CD274
| 2
OTUD1 phosphorylates CD274.
| 1
OTUD1 leads to the phosphorylation of CD274. 1 / 1
| 1

reach
"In addition, in mice with breast cancer (97), the number of infiltrating CD8 T cells and the serum levels of IFN-γ were significantly increased after PD-L1 destabilization induced by OTUD1 deletion, promoting tumor immunotherapy.3.4 Phosphorylation of PD-L1."
OTUD1 dephosphorylates CD274.
| 1
OTUD1 leads to the dephosphorylation of CD274. 1 / 1
| 1

reach
"In addition, in mice with breast cancer (97), the number of infiltrating CD8 T cells and the serum levels of IFN-γ were significantly increased after PD-L1 destabilization induced by OTUD1 deletion, promoting tumor immunotherapy.3.4 Phosphorylation of PD-L1."
OTUD1 affects BCL2
| 2
OTUD1 inhibits BCL2. 2 / 2
| 2

reach
"Keeping in line with these results, Otud1 overexpression suppressed the upregulation of pro-apoptotic proteins and prevented the reduction of anti-apoptotic protein Bcl2 caused by H/R treatment (Fig. S5G)."

reach
"In addition, Nrf2 deletion impaired Otud1 ability in reducing pro-apoptotic proteins and elevating anti-apoptotic protein Bcl2 in H/R-stimulated primary hepatocytes (Fig. S7A)."
OTUD1 affects ASK1-p38
| 2
OTUD1 activates ASK1-p38. 2 / 2
| 2

reach
"These results demonstrate that OTUD1 activates the ASK1-p38/JNK signaling pathway in response to pro-hypertrophy stimulation."

reach
"OTUD1 activates the ASK1-p38/JNK pathways during cardiac hypertrophy."
NOTCH2 affects OTUD1
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2 |

No evidence text available

No evidence text available
K33 affects OTUD1
| 2
OTUD1 binds CARD9 and K33. 2 / 2
| 2

reach
"32 We demonstrate that OTUD1 binds to the CARD9 and removes the K33‐linked ubiquitin from CARD9, thus promoting the assembly of the CBM complex in macrophages upon ISO stimulation."

reach
"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability."
JNK affects OTUD1
| 2
JNK increases the amount of OTUD1.
| 1
Phosphorylated JNK increases the amount of OTUD1. 1 / 1
| 1

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"Our data showed the significant activation of Ask1 in Otud1-overexpressed hearts, alongside increased phosphorylation of p38 and JNK."
JNK activates OTUD1.
| 1
JNK activates OTUD1. 1 / 1
| 1

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"ASK1/JNK pathway inhibitors effectively suppressed OTUD1-mediated OSCS."
IREB2 affects OTUD1
| 1 1
| 1 1

reach
"Studies have shown that in colon cancer, OTUD1 can bind and promote the deubiquitination modification of IREB2 (iron-responsive element-binding protein2), a primary regulator of iron metabolism."

sparser
"Song et al. showed that OTUD1 binds IREB2 through the N-terminal APGR, and deubiquitinates K48- and K63-linked ubiquitin chains from IREB2."
HRAS affects OTUD1
| 2
HRAS decreases the amount of OTUD1. 2 / 2
| 2

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"Similar as the BRCA1 and BRCA2 tumor suppressors, expression of OTUD1 was significantly suppressed by wild-type HRAS in p53 null MCF10A cells, but not in the control MCF10A cells (p53-wt), indicating that gain of oncogenic RAS together with loss of p53 tumor suppressor could lead to decreased OTUD1 function (GSE81593)."

reach
"Consistent with the notion that activation of HRAS inhibits OTUD1 expression in p53 mutant cells, we found that upon ectopic expression of constitutively active HRASV12, OTUD1 is downregulated in p53 mutant MDA-MB-231 (both the early passage and the bone-metastatic (BM) cell lines) but not in p53 wt MCF7 cells, TGF-beta and HRAS collaborate to promote EMT, invasion and cancer stem traits in breast cancer cells 36."
DDIT3 affects OTUD1
| 2
DDIT3 increases the amount of OTUD1. 2 / 2
| 2

reach
"Importantly, DDIT3 induced OTU deubiquitinase 1 (OTUD1) expression by activating the NF-kappaB signaling pathway, thus increasing intracellular Smurf1 protein levels to degrade MAVS and inhibit IFN-I production during BVDV infection."

reach
"DDIT3 promoted NF-kappaB-dependent OTU deubiquitinase 1 (OTUD1) expression."
CDKN2A affects OTUD1
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2 |

No evidence text available

No evidence text available
CDK9 affects OTUD1
| 1 1
| 1 1

sparser
"In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells."

reach
"In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells."
CARD9 affects K33, and OTUD1
| 2
OTUD1 binds CARD9 and K33. 2 / 2
| 2

reach
"32 We demonstrate that OTUD1 binds to the CARD9 and removes the K33‐linked ubiquitin from CARD9, thus promoting the assembly of the CBM complex in macrophages upon ISO stimulation."

reach
"We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33-linked ubiquitin from CARD9 to promote the assembly of the CARD9-BCL10-MALT1 (CBM) complex, without affecting CARD9 stability."
BCL2L11 affects OTUD1
1 | 1
1 | 1

sparser
"OTUD1 directly interacted with Bim and inhibited its ubiquitination."

No evidence text available
2 |
Air Pollutants increases the amount of OTUD1.
1 |
Air Pollutants increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Air Pollutants decreases the amount of OTUD1.
1 |
Air Pollutants decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
2 |

No evidence text available

No evidence text available
1 |
Valproic acid increases the amount of OTUD1. 1 / 1
1 |

No evidence text available

No evidence text available
1 |
Thioacetamide increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Testosterone decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Sulindac affects OTUD1
1 |
Sulindac increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Sodium arsenite increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Si-OTUD1-2 affects OTUD1
| 1
Si-OTUD1-2 decreases the amount of OTUD1. 1 / 1
| 1

reach
"The result demonstrated that OTUD1 expression was significantly reduced by both si-OTUD1-2 and si-OTUD1-3 (P < 0.01, Figure 1)."
Ppy affects OTUD1
| 1
| 1

sparser
"As shown in Figure 3 E, WT Akt PH interacted with OTUD1, while either mutant K14A or R25A showed decreased affinity."
1 |
Pirinixic acid increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Phenformin affects OTUD1
1 |
Phenformin decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Peptide affects OTUD1
| 1
Peptide binds OTUD1-C320R. 1 / 1
| 1

reach
"HEK 293 cells expressing N-terminally Streptavidin-Binding Peptide (SBP)-tagged OTUD1 C320R and C320R/ΔETGE mutants were lysed as for immunoprecipitation experiments."
P38 affects OTUD1
| 1
Phosphorylated p38 increases the amount of OTUD1. 1 / 1
| 1

reach
"Our data showed the significant activation of Ask1 in Otud1-overexpressed hearts, alongside increased phosphorylation of p38 and JNK."
Ozone affects OTUD1
1 |
Ozone increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Ovarian tumor domain affects OTUD1
| 1
Ovarian tumor domain activates OTUD1. 1 / 1
| 1

eidos
"Moreover , the ovarian tumor domain allows the OTUD1 to separate IRF3 from the promoter region of the target gene and inhibits the normal production of interferon , while it does not affect the normal dimerization of IRF3 and translocate into the nucleus ."
1 |
Nickel sulfate increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Methyltestosterone increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Methyl methanesulfonate increases the amount of OTUD1. 1 / 1
1 |

No evidence text available

reach
"Consistent with the former investigations that IRF3 promoted inflammatory responses in LPS induced sepsis, Otud1 -/- mice were more susceptible to LPS stimulation."
1 |
Indole-3-methanol increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Ibrutinib affects OTUD1
| 1
| 1

reach
"The FDA-approved drug ibrutinib preferentially reduces the tumorigenicity of OTUD1 high ovarian cancer cells."
1 |
Hsa-mir-4329 decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-mir-4262 decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6761-5p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-506-3p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3613-3p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-335-5p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-21-5p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-181b-5p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-124-3p decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Glucose affects OTUD1
| 1
Glucose decreases the amount of OTUD1. 1 / 1
| 1

reach
"Glucose at the concentration of 100 mmol/L significantly induced the mRNA expression of OTUD1 (P < 0.05), but significantly decreased the OTUD1 protein level (P < 0.05) (Figures 2E-F)."
Ethanol affects OTUD1
1 |
Ethanol decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Drug affects OTUD1
| 1
Drug activates OTUD1. 1 / 1
| 1

eidos
"Bioinformatics analyses and western blot were applied for investigating OTUD1 expression in lung cancer and the drug that upregulated OTUD1 ."
1 |
Dorsomorphin decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Dibutyl phthalate increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Coumestrol affects OTUD1
1 |
Coumestrol decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Copper atom affects OTUD1
1 |
Copper atom increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Benzene-1,2,4-triol increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
All-trans-retinoic acid increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
Actinomycin D increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
ZNF598 affects OTUD1
1 |
1 |

No evidence text available
YWHAQ affects OTUD1
1 |
1 |

No evidence text available
YOD1 affects OTUD1
| 1
YOD1 inhibits OTUD1. 1 / 1
| 1

reach
"OTUD1 is negatively regulated by miR-4429 in ovarian cancer, and the expression of YOD1 increases when miR-4429 is reduced, promoting the growth and metastasis of ovarian cancer."
YBX3 affects OTUD1
1 |
1 |

No evidence text available
XRCC6 affects OTUD1
1 |
1 |

No evidence text available
WIZ affects OTUD1
1 |
1 |

No evidence text available
VIM affects OTUD1
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
| 1

sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
VE-822 affects OTUD1
| 1
VE-822 activates OTUD1. 1 / 1
| 1

reach
"VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma."
VDAC2 affects OTUD1
1 |
1 |

No evidence text available
USP11 affects OTUD1
1 |
1 |

No evidence text available
Tobacco Smoke Pollution decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
TRIM25 affects OTUD1
1 |
1 |

No evidence text available
TRAF6 affects MAVS
| 1
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
TOMM20 affects OTUD1
1 |
1 |

No evidence text available
TNRC6B affects OTUD1
1 |
1 |

No evidence text available
TNF affects OTUD1
1 |
1 |

No evidence text available
TMPO affects OTUD1
1 |
1 |

No evidence text available
TMEM165 affects OTUD1
1 |
1 |

No evidence text available
TGFB affects OTUD1
| 1
TGFB activates OTUD1. 1 / 1
| 1

reach
"This latter effect is inhibited by the treatment of SB431542, a selective TbetaRI kinase inhibitor, suggesting that the autocrine TGF-beta is sufficient to promote EMT in OTUD1 depleted cells."
TECR affects OTUD1
1 |
1 |

No evidence text available
TCP1 affects OTUD1
1 |
1 |

No evidence text available
TARS1 affects OTUD1
1 |
1 |

No evidence text available
TAFAZZIN affects OTUD1
| 1
| 1

reach
"In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1."
Stroke affects OTUD1
| 1
Stroke activates OTUD1. 1 / 1
| 1

reach
"Herpesvirus latent infection promotes stroke via activating the OTUD1/NF-kappaB signaling pathway."
SNW1 affects OTUD1
1 |
1 |

No evidence text available
SNAI1 affects OTUD1
1 |
1 |

No evidence text available
SKP2 affects OTUD1
| 1
| 1

sparser
"To assess whether the expression of SKP2 or OTUD1 is associated with clinical outcomes in breast cancer patients, we performed Kaplan–Meier (KM) plotter analysis of microarray datasets of human mammary tumors xref ."
SF3B2 affects OTUD1
1 |
1 |

No evidence text available
1 |

No evidence text available
RSL1D1 affects OTUD1
1 |
1 |

No evidence text available
RPN1 affects OTUD1
1 |
1 |

No evidence text available
RPL23 affects OTUD1
1 |
1 |

No evidence text available
RPL17 affects OTUD1
1 |
1 |

No evidence text available
RPL13A affects OTUD1
1 |
1 |

No evidence text available
RPL10 affects OTUD1
1 |
1 |

No evidence text available
RELA affects OTUD1
| 1
RELA inhibits OTUD1. 1 / 1
| 1

reach
"OTUD1-promoter-luciferase (OTUD1-luc) activity was decreased by knockdown of p65 in MC38, HT29 and 293T cells analyzed by the luciferase reporter assay, and vice versa (Fig. 5D, E, S4A, B)."
RBBP4 affects OTUD1
1 |
1 |

No evidence text available
RAD23A affects OTUD1
1 |
1 |

No evidence text available
RAB11FIP5 affects OTUD1
| 1

sparser
"Mechanistically, LC-MS/MS and Co-IP studies showed that OTUD1 bound directly to the GAF1 and PDEase domains of PDE5A."
Particulate Matter increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
PSMD3 affects OTUD1
1 |
1 |

No evidence text available
PSMC5 affects OTUD1
1 |
1 |

No evidence text available
PSMC2 affects OTUD1
1 |
1 |

No evidence text available
PRRC2B affects OTUD1
1 |
1 |

No evidence text available
PRPS2 affects OTUD1
1 |
1 |

No evidence text available
PRMT1 affects OTUD1
1 |
1 |

No evidence text available
PRDX1 affects OTUD1
1 |
1 |

No evidence text available
PPP2R2A affects OTUD1
1 |
1 |

No evidence text available
PPP2R1A affects OTUD1
1 |
1 |

No evidence text available
POU5F1 affects OTUD1
| 1
POU5F1 inhibits OTUD1. 1 / 1
| 1

reach
"In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1."
POLR2H affects OTUD1
1 |
1 |

No evidence text available
PKM affects OTUD1
1 |
1 |

No evidence text available
PGAM5 affects 293T
| 1
OTUD1 binds PGAM5 and 293T. 1 / 1
| 1

reach
"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure 6C-D)."
PCI 5002 affects OTUD1
1 |
PCI 5002 increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
PABPC1 affects OTUD1
1 |
1 |

No evidence text available
1 |
1 |

No evidence text available
| 1

reach
"Finally, pharmacological inhibition of β-catenin reversed the improvement of delayed wound healing induced by OTUD1 knockdown in db/db mice."

reach
"In both RNA and DNA virus infections, OTUD1 inhibits IRF3-dependent type I IFN production [ 22 ]."
OTUD1 affects signaling
| 1
OTUD1 inhibits signaling. 1 / 1
| 1

sparser
"We next investigated the molecular mechanism by which OTUD1 inhibits TGF-β/SMAD signaling."
OTUD1 affects self-ubiquitination
| 1
OTUD1 inhibits self-ubiquitination. 1 / 1
| 1

eidos
"OTUD1 interacts with Smurf1 and functions as a deubiquitinase to remove the K48-linked ubiquitination of Smurf1 , prevent its self-ubiquitination degradation , and upregulate its protein level ; whereas the binding of Ndfip1 to MAVS recruits Smurf1 to MAVS , and the interaction between Ndfip1 and Smurf1 enhances the self-ubiquitination ( possibly k63-linked ) and enzyme activity of Smurf1 ( Table 1 ) ( 47 , 49 ) ."
OTUD1 affects release molecular patterns
| 1
OTUD1 inhibits release molecular patterns. 1 / 1
| 1

eidos
"Moreover , the presence of OTUD1 promotes the release of damage-associated molecular patterns ( DAMPs ) , which in turn recruits the leukocytes and strengthens host immune response ."
OTUD1 affects recruitment NF-kappaB essential modulator
| 1
OTUD1 inhibits recruitment NF-kappaB essential modulator. 1 / 1
| 1

eidos
"Mechanistically , OTUD1 physically interacts with receptor-interacting serine / threonine-protein kinase 1 ( RIPK1 ) and selectively cleaves K63-linked polyubiquitin chains from RIPK1 to inhibit the recruitment of NF-kappaB essential modulator ( NEMO ) ."

reach
"OTUD1 deubiquitinase regulates NF-kappaB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways."

reach
"All the above results demonstrated that OTUD1-based aggresomes contribute to ASK1 protein stabilization and persistent ASK1/JNK activation and that this function is mediated by a region (aa 105–164) located in the OTUD1 N-terminal intrinsically disordered region."
OTUD1 affects proteasome inhibitors
| 1
OTUD1 inhibits proteasome inhibitors. 1 / 1
| 1

reach
"Furthermore, OTUD1 modulates intracellular Ig-light chain production and sensitivity to proteasome inhibitors in plasma cells."
OTUD1 affects proinflammatory cytokine
| 1
OTUD1 activates proinflammatory cytokine. 1 / 1
| 1

eidos
"OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation ."
OTUD1 affects ppy
| 1
| 1

sparser
"As shown in Figure 3 E, WT Akt PH interacted with OTUD1, while either mutant K14A or R25A showed decreased affinity."
OTUD1 affects polyubiquitination
| 1
OTUD1 inhibits polyubiquitination. 1 / 1
| 1

sparser
"However, specific protein substrates whose K63-linked polyubiquitination is inhibited by OTUD1 remain unknown."
OTUD1 affects peptide
| 1
Peptide binds OTUD1-C320R. 1 / 1
| 1

reach
"HEK 293 cells expressing N-terminally Streptavidin-Binding Peptide (SBP)-tagged OTUD1 C320R and C320R/ΔETGE mutants were lysed as for immunoprecipitation experiments."
OTUD1 affects pathways
| 1
OTUD1 activates pathways. 1 / 1
| 1

sparser
"OTUD1 activates the ASK1-p38/JNK pathways during cardiac hypertrophy."
OTUD1 affects navitoclax
| 1
| 1

reach
"Knockdown of OTUD1 increases the sensitivity of tumour cells to the BH3-mimetic inhibitor ABT-263, while overexpression of OTUD1 increases tumour cell tolerance of ABT-263."
OTUD1 affects melatonin-induced Bim
| 1
OTUD1 activates melatonin-induced Bim. 1 / 1
| 1

eidos
"OTUD1 knockdown inhibited melatonin-induced Bim upregulation and apoptosis in cancer cells ."
OTUD1 affects iron atom
| 1
| 1

reach
"The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity."
OTUD1 affects interferon-mediated disease128
| 1
OTUD1 inhibits interferon-mediated disease128. 1 / 1
| 1

eidos
"In experiments in vitro and in vivo in mice , OTUD1 repressed type I interferon-mediated disease128 ."
OTUD1 affects interferon IFN antiviral pathway
| 1
OTUD1 activates interferon IFN antiviral pathway. 1 / 1
| 1

eidos
"OTUD1 negatively regulates the canonical NF-kappaB activation , apoptosis , and necroptosis , whereas OTUD1 upregulates the interferon ( IFN ) antiviral pathway ."

reach
"OTUD1 can inhibit the transcriptome activity of IRF3, thus maintaining immune homeostasis in cells and hence dose OTUD3, PTUD4, and A20 (16, 24–26)."
OTUD1 affects function OTUD1
| 1
OTUD1 inhibits function OTUD1. 1 / 1
| 1

eidos
"OTUD1 ( Ovarian Tumor Family Deubiquitinase 1 , FDR = 3.74 x 10-13 ) can inhibit nuclear translocation and transcriptional activity of the IFNgamma-activated transcription factor IRF3 ( Lu et al ., 2018 ) , and loss of function of OTUD1 is associated with auto-immune diseases mediated by interferons ( Lu et al ., 2018 ) ."

reach
"OTUD1-driven NICD signaling promoted the differentiation and functions of Th1 and Th17 cells and amplified the cascade of aGVHD."
OTUD1 affects ccRCC
| 1
OTUD1 inhibits ccRCC. 1 / 1
| 1

reach
"Reduced expression of OTUD1 in renal cancer patients raises PTEN ubiquitination degradation, which stimulates the TNF-α/NF-κB and PI3K/AKT signaling pathways, encourages the growth of ccRCC, and influences patient prognosis."
OTUD1 affects cancer cells
| 1
OTUD1 activates cancer cells. 1 / 1
| 1

eidos
"OTUD1 knockdown inhibited melatonin-induced Bim upregulation and apoptosis in cancer cells ."
OTUD1 affects cancer cell growth
| 1
OTUD1 inhibits cancer cell growth. 1 / 1
| 1

eidos
"Then , we showed that OTUD1 inhibits cancer cell growth ."
OTUD1 affects activation
| 1
OTUD1 inhibits activation. 1 / 1
| 1

sparser
"Results showed that knockdown of OTUD1 significantly enhanced activation of IFNβ promoter during SeV infection ( xref ), and overexpression of OTUD1 inhibited SeV-induced activation of IFNβ promoter ( xref )."
OTUD1 affects ZNF598
1 |
1 |

No evidence text available
OTUD1 affects YWHAQ
1 |
1 |

No evidence text available
OTUD1 affects YBX3
1 |
1 |

No evidence text available
OTUD1 affects XRCC6
1 |
1 |

No evidence text available
OTUD1 affects WIZ
1 |
1 |

No evidence text available
OTUD1 affects VDAC2
1 |
1 |

No evidence text available
OTUD1 affects USP4
| 1
OTUD1 inhibits USP4. 1 / 1
| 1

reach
"This suggests that Ang II, in addition to increasing OTUD1, may supress USP4."
OTUD1 affects USP11
1 |
1 |

No evidence text available
OTUD1 affects TRIM25
1 |
1 |

No evidence text available
OTUD1 affects TOMM20
1 |
1 |

No evidence text available
OTUD1 affects TNRC6B
1 |
1 |

No evidence text available
OTUD1 affects TMPO
1 |
1 |

No evidence text available
OTUD1 affects TMEM165
1 |
1 |

No evidence text available
OTUD1 affects TGM1
| 1
OTUD1 activates TGM1. 1 / 1
| 1

reach
"For example, OTUD1 can enhance the stability of fibrinogen-like protein 1 in liver microenvironment and thus regulate tumor progression via tumor associated macrophages-OTUD1- fibrinogen-like protein 1 axis (Li et al., 2023a); moreover, OTUD1 can serve a negative prognostic factor for hepatocellular carcinoma (Wu et al., 2019)."
OTUD1 affects TECR
1 |
1 |

No evidence text available
OTUD1 affects TCP1
1 |
1 |

No evidence text available
OTUD1 affects TARS1
1 |
1 |

No evidence text available
OTUD1 affects Smurf1-MAVS/TRAF3/TRAF6
| 1
OTUD1 inhibits Smurf1-MAVS/TRAF3/TRAF6. 1 / 1
| 1

reach
"Finally, the deubiquitinase OTUD1 potently inhibits RLR pathway by utilizing Smurf1-MAVS/TRAF3/TRAF6 signaling at the early stage of viral infection."
OTUD1 affects SNW1
1 |
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No evidence text available
OTUD1 affects SNAI1
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No evidence text available
OTUD1 affects SF3B2
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No evidence text available
OTUD1 affects SCF SKP2
| 1
OTUD1 inhibits SCF SKP2. 1 / 1
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"Here, we report that YAP is subject to non proteolytic, K63 linked polyubiquitination by the SCF SKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1."
OTUD1 affects S phase
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OTUD1 activates S phase. 1 / 1
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"Further analysis revealed that OTUD1 oe induced partial arrest in the S phase of the cell cycle without affecting cell viability (Supplementary Fig. 2h, i)."

reach
"Consistently, Otud1 overexpression led to a decrease of ROS in I/R-challenged liver samples (Fig. S4B)."
OTUD1 affects Release
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OTUD1 activates Release. 1 / 1
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"OTUD1 Potentiates the Inhibitory Effects of BST-2 on HIV-1 Release."
OTUD1 affects RSL1D1
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No evidence text available
OTUD1 affects RPN1
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No evidence text available
OTUD1 affects RPL23
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1 |

No evidence text available
OTUD1 affects RPL17
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No evidence text available
OTUD1 affects RPL13A
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No evidence text available
OTUD1 affects RPL10
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No evidence text available
OTUD1 affects RBBP4
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1 |

No evidence text available
OTUD1 affects RAS
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OTUD1 activates RAS. 1 / 1
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"Depletion of endogenous OTUD1 potentiated the capacity of RAS transformed MCF10A cells to form tumor organoids in 3D Matrigel but did not inhibit tumor cell survival and proliferation under standard 2D culture conditions."
OTUD1 affects RAD23A
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No evidence text available
OTUD1 affects RAB11FIP5
| 1

sparser
"Mechanistically, LC-MS/MS and Co-IP studies showed that OTUD1 bound directly to the GAF1 and PDEase domains of PDE5A."
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"In short, OTUD1 prefers abolishing proteosome-mediated NRF2 degradation rather than modulating NRF2 function through removing K63 polyubiquitin scaffold.Due to its robust cytoprotective role in preventing oxidative stress and inflammation, NRF2 activation is considered a promising therapeutic strategy for numerous diseases characterized by oxidative stress [40]."
OTUD1 affects PSMD3
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No evidence text available
OTUD1 affects PSMC5
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No evidence text available
OTUD1 affects PSMC2
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No evidence text available
OTUD1 affects PRRC2B
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1 |

No evidence text available
OTUD1 affects PRPS2
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No evidence text available
OTUD1 affects PRMT1
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No evidence text available
OTUD1 affects PRDX1
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No evidence text available
OTUD1 affects PPP2R2A
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No evidence text available
OTUD1 affects PPP2R1A
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No evidence text available
OTUD1 affects POLR2H
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No evidence text available
OTUD1 affects PKM
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No evidence text available
OTUD1 affects PI3K
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OTUD1 inhibits PI3K. 1 / 1
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"OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs."
OTUD1 affects PARP1
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OTUD1 activates PARP1. 1 / 1
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"Moreover, OTUD1 overexpression promoted the cleavage of caspase-3 and PARP, which are apoptotic indicators, and increased apoptosis."
OTUD1 affects PABPC1
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No evidence text available
OTUD1 affects OSCS maintenance
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OTUD1 inhibits OSCS maintenance. 1 / 1
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"Indeed, our results showed that OTUD1 expression reduced the sensitivity of SKOV3, OVCAR8 and CAOV3 cells to cisplatin treatment, most likely by promoting OSCS maintenance (Fig. 6h, i, Supplementary Figs."
OTUD1 affects NUP153
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No evidence text available
OTUD1 affects NOP2
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No evidence text available
OTUD1 affects NDUFA10
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1 |

No evidence text available
OTUD1 affects MYC
| 1
| 1

sparser
"We transfected hemagglutinin (HA)‐Ub, OTUD1Myc and KLF4‐3 × flag into 293T cells, followed by introduction of the proteasome inhibitor MG132 to treat cells for preventing protein degradation."
OTUD1 affects METTL3
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sparser
"METTL3 could directly interact with OTUD1 mRNA (Figure xref D)."
OTUD1 affects MCM7
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No evidence text available
OTUD1 affects MCM5
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No evidence text available
OTUD1 affects MCM3
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No evidence text available
OTUD1 affects MCF10A cells expressing RAS metastasis breast cancer cells mice
| 1
OTUD1 inhibits MCF10A cells expressing RAS metastasis breast cancer cells mice. 1 / 1
| 1

eidos
"Moreover , OTUD1 suppresses TGF-beta signaling and EMT in MCF10A cells expressing RAS and metastasis of breast cancer cells in mice , respectively , presumably through deubiquitylating SMAD7 thus enabling SMURF2 binding and subsequent TGFR turnover43 ."
OTUD1 affects MAVS/TRAF3/TRAF6
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OTUD1 inhibits MAVS/TRAF3/TRAF6. 1 / 1
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"As a consequence, OTUD1 inhibits MAVS/TRAF3/TRAF6 signalosome mediated production of type I IFNs and proinflammatory cytokines during RNA virus infection (XREF_FIG)."
OTUD1 affects MAVS/TRAF3/TRAF6 signalosome
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OTUD1 activates MAVS/TRAF3/TRAF6 signalosome. 1 / 1
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"Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome."
OTUD1 affects MAVS/TRAF3/TRAF6 signalosome proteins
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OTUD1 inhibits MAVS/TRAF3/TRAF6 signalosome proteins. 1 / 1
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"Taken together, these data suggest that OTUD1 is responsible for downregulation of both MAVS/TRAF3/TRAF6 signalosome proteins and subsequent production of IFNbeta mRNA at the early stage of RNA virus infection."
OTUD1 affects MAVS/TRAF3/TRAF6 proteins
| 1
OTUD1 activates MAVS/TRAF3/TRAF6 proteins. 1 / 1
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"Importantly, OTUD1 contributes to RNA virus induced downregulation of MAVS/TRAF3/TRAF6 proteins."
OTUD1 affects MAVS/TRAF3/TRAF6 protein
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OTUD1 decreases the amount of MAVS/TRAF3/TRAF6 protein. 1 / 1
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"Given that OTUD1 downregulated MAVS/TRAF3/TRAF6 protein levels, we next questioned whether OTUD1 could inhibit MAVS/TRAF3/TRAF6 signalosome mediated IFNs production and antiviral activity."
OTUD1 affects MAPK
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OTUD1 inhibits MAPK. 1 / 1
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"Importantly, in vivo and in vitro, OTUD1 was shown to negatively regulate inflammatory responses and play a protective role in sepsis-induced pathological lung injury by mechanistically inhibiting the activation of the transforming growth factor-beta-activated kinase 1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in the present study."
OTUD1 affects MAP3K7
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OTUD1 inhibits MAP3K7. 1 / 1
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"Importantly, in vivo and in vitro, OTUD1 was shown to negatively regulate inflammatory responses and play a protective role in sepsis-induced pathological lung injury by mechanistically inhibiting the activation of the transforming growth factor-beta-activated kinase 1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in the present study."
OTUD1 affects Klk9
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sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
OTUD1 affects KL4
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OTUD1 inhibits KL4. 1 / 1
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"Nevertheless, knockdown of OTUD1 dramatically reduced the KLF4 half‐lives (Figure 5c,d), which suggested that OTUD1 reduced the degradation of KL4."
OTUD1 affects K63
| 1
OTUD1 binds IRF3 and K63. 1 / 1
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"As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63 linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity."
OTUD1 affects K48-linked polyubiquitination Tyk2
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OTUD1 inhibits K48-linked polyubiquitination Tyk2. 1 / 1
| 1

eidos
"OTUD1 inhibits K48-linked polyubiquitination of Tyk2 dependently on AHI1 ."
OTUD1 affects Ischemia
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"Applying multiple experimental approaches and using both in vitro and in vivo models, our present study showed that protein level of RIP2 and OTUD1 were elevated noticeably in cerebral ischemia induced by MCAO, primary cultured astrocytes and BV2 cells subjected to OGD/R."

reach
"Taken together, these findings indicate that OTUD1 is a suppressor of the NF-κB signaling pathway, and the aberrant OTUD1 activity induces inflammatory bowel diseases such as UC by the hyperactivation of the NF-κB pathway."

reach
"Furthermore, quite recently OTUD1 was found to suppress IBD by removing the K63 ubiquitin chain from RIP1 [28]."
OTUD1 affects IgL
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OTUD1 activates IgL. 1 / 1
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"OTUD1 modulates IgL production, proteasome load and PI sensitivity."
OTUD1 affects ISRE promoter
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OTUD1 inhibits ISRE promoter. 1 / 1
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"And exogenous expression of OTUD1 lowered SeV induced ISRE promoter activity (XREF_SUPPLEMENTARY)."
OTUD1 affects IRS4
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No evidence text available
OTUD1 affects IRF7
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No evidence text available
OTUD1 affects IRF3/7
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OTUD1 inhibits IRF3/7. 1 / 1
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"To conclude, our research has brought to light for the first time in teleost that OTUD1 degrade IRF3/7 through decreasing their ubiquitination, thereby restraining IRF3/7-mediated antiviral immune response, which provides an important reference for the study of teleost interferon signaling."
OTUD1 affects IP6K2
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No evidence text available
OTUD1 affects IL6
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OTUD1 activates IL6. 1 / 1
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"At day 3 after VSV infection, Otud1 -/- mice produced much higher expression of IFNbeta and IL-6 mRNAs (XREF_FIG), and had much lower viral RNAs (XREF_FIG) in their lung tissue than did Otud1 +/+ mice."
OTUD1 affects IFN-I
| 1
OTUD1 inhibits IFN-I. 1 / 1
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"Importantly, DDIT3 induced OTU deubiquitinase 1 (OTUD1) expression by activating the NF-kappaB signaling pathway, thus increasing intracellular Smurf1 protein levels to degrade MAVS and inhibit IFN-I production during BVDV infection."
OTUD1 affects IBA57
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No evidence text available
OTUD1 affects HSPA4
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No evidence text available
OTUD1 affects HSP90AB1
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No evidence text available
OTUD1 affects H9c2
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OTUD1 inhibits H9c2. 1 / 1
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"Notably, OTUD1 expression was significantly decreased in BECN1-overexpressing H9c2 cells ( p < 0.05, Fig. 8 )."
OTUD1 affects H3-5
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No evidence text available
OTUD1 affects GTF2I
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No evidence text available
OTUD1 affects Figures 2E-F
| 1
OTUD1 inhibits Figures 2E-F. 1 / 1
| 1

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"Glucose at the concentration of 100 mmol/L significantly induced the mRNA expression of OTUD1 (P < 0.05), but significantly decreased the OTUD1 protein level (P < 0.05) (Figures 2E-F)."
OTUD1 affects FN1
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
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sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
OTUD1 affects FARSA
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No evidence text available
OTUD1 affects ERBB2
| 1
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sparser
"Furthermore, higher OTUD1 expression was significantly associated with low recurrence-free survival of HER2 + non-luminal subtype of breast cancer patients and EMT subtype of cervical cancer patients (Fig.  xref c, d)."
OTUD1 affects EIF3A
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No evidence text available
OTUD1 affects EIF2S1
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No evidence text available
OTUD1 affects EEF1G
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1 |

No evidence text available
OTUD1 affects EEA1
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No evidence text available
OTUD1 affects E3 ubiquitin ligase Smurf1
| 1
OTUD1 activates E3 ubiquitin ligase Smurf1. 1 / 1
| 1

eidos
"Furthermore , OTUD1 induced upregulation of the E3 ubiquitin ligase Smurf1 by deubiquitinating Smurf1 , and Smurf1 degraded MAVS in MDBK cells in a ubiquitination-dependent manner , ultimately inhibiting IFN-I production ."
OTUD1 affects Dnmt1
| 1
| 1

sparser
"Moreover, we observed that p53 showed better interaction with the UIM-lacking OTUD1 1-450 mutant than with WT OTUD1."
OTUD1 affects DNAJA1
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No evidence text available
OTUD1 affects DNA repair
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"OTUD1 inhibits DNA repair by inhibiting the activity of Ubc13/RNF168."
OTUD1 affects DHRS7B
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1 |

No evidence text available
OTUD1 affects ChFP
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OTUD1 activates ChFP. 1 / 1
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"OTUB2, OTUD3, USP10 and UCHL1 expression did not alter the ChFP:GFP ratio of the control reporter while OTUD1 and USP21 only modestly elevated the ChFP:GFP ratio indicating that the identified Dubs specifically alter the ability of ribosomes to progress through a poly(A)-induced ribosomal stall (Figure 3B)."
OTUD1 affects Caspase-Independent Caspase-Dependent Apoptosis
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OTUD1 activates Caspase-Independent Caspase-Dependent Apoptosis. 1 / 1
| 1

eidos
"OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation ."
OTUD1 affects Caspase
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OTUD1 activates Caspase. 1 / 1
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"OTUD1 can activate caspase-dependent apoptosis, with interaction between C-Caspase-3 and C-Caspase-9 [ 37 ]; however, this phenomenon has only been proven in esophageal carcinoma and renal carcinoma [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD1 affects CUL3
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No evidence text available
OTUD1 affects CHCHD4
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1 |

No evidence text available
OTUD1 affects CDKN2AIP
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No evidence text available
OTUD1 affects CDK1
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1 |

No evidence text available
OTUD1 affects CDH1
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
| 1

sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
OTUD1 affects CCT8
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1 |

No evidence text available
OTUD1 affects CCT3
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1 |

No evidence text available
OTUD1 affects CASP3
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OTUD1 activates CASP3. 1 / 1
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"Moreover, OTUD1 overexpression promoted the cleavage of caspase-3 and PARP, which are apoptotic indicators, and increased apoptosis."
OTUD1 affects CAPRIN1
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1 |

No evidence text available
OTUD1 affects CAD
1 |
1 |

No evidence text available
OTUD1 affects C1QBP
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1 |

No evidence text available
OTUD1 affects BRD9
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1 |

No evidence text available
OTUD1 affects BRCA1
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OTUD1 activates BRCA1. 1 / 1
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"Intriguingly, we observed that the 70 core targets of tumor suppressor Breast Cancer 1 (BRCA1) are all significantly enriched in OTUD1-high patients, strongly indicating that OTUD1 could support BRCA1 function."
OTUD1 affects BECN1
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OTUD1 inhibits BECN1. 1 / 1
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"The findings of the present study fill this gap by revealing that OTUD1 deubiquitination can be decreased by upregulating BECN1; immunofluorescence analysis results are consistent with this finding ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
OTUD1 affects BAG6
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No evidence text available

reach
"The ATR inhibitor VE-822 upregulates the expression level of the deubiquitinating enzyme OTUD1 to stabilize FHL1 expression through its OUT domain and inhibits the progression of lung adenocarcinoma."
OTUD1 affects ATP5PO
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No evidence text available
OTUD1 affects ANXA4
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OTUD1 leads to the deubiquitination of ANXA4. 1 / 1
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"Mechanistically, OTUD1 suppressed the process of protein endoplasmic reticulum‐to‐Golgi trafficking by removing k63‐linked ubiquitination of Sec23 homologue B (SEC23B), a coat protein II complex component."
OTUD1 affects AKT3
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1 |

No evidence text available
OTUD1 affects AKT2
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1 |

No evidence text available
OTUD1 affects AHI1-mediated Tyk2
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OTUD1 activates AHI1-mediated Tyk2. 1 / 1
| 1

eidos
"Importantly , OTUD1 knockdown inhibited the AHI1-mediated upregulation of Tyk2 levels ( Fig. 4e ) , suggesting that OTUD1 is essential for the AHI1-mediated regulation of Tyk2 protein levels ."
OTUD1 affects ACTG2
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No evidence text available
OTUD1 affects ACBD3
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1 |

No evidence text available
OTUD1 affects AAAS
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1 |

No evidence text available
OTUD1 affects 293T
| 1
OTUD1 binds PGAM5 and 293T. 1 / 1
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"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure 6C-D)."
Nitrates affects OTUD1
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Nitrates increases the amount of OTUD1. 1 / 1
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No evidence text available
Neoplasms affects OTUD1
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Neoplasms increases the amount of OTUD1. 1 / 1
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"Mechanistically, tumor-associated macrophages (TAMs) activate NF-kB by secreting TNFalpha/IL-1beta in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination."
NUP153 affects OTUD1
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1 |

No evidence text available
NSC 689534 affects OTUD1
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NSC 689534 increases the amount of OTUD1. 1 / 1
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No evidence text available
NOP2 affects OTUD1
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1 |

No evidence text available
NFkappaB affects OTUD1
| 1

sparser
"Studies have shown that OTUD1 interacts with NF-κB and interferes with the inflammatory response involved in NF-κB, thereby affecting the homeostatic environment in brain cells."
NF-ĸB/p65 affects OTUD1
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NF-ĸB/p65 activates OTUD1. 1 / 1
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"These data suggest that TAM-mediated NF-ĸB/p65 activation transcriptionally upregulates OTUD1."
NDUFA10 affects OTUD1
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1 |

No evidence text available
NANOG affects OTUD1
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NANOG inhibits OTUD1. 1 / 1
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"In line with this, the transcription of the pluripotency factors NANOG, SOX2, OCT4, and TAZ were significantly elevated in OTUD1 depleted tumors and severely inhibited in tumors expressing wild-type OTUD1."
MYC affects OTUD1
| 1
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sparser
"We transfected hemagglutinin (HA)‐Ub, OTUD1Myc and KLF4‐3 × flag into 293T cells, followed by introduction of the proteasome inhibitor MG132 to treat cells for preventing protein degradation."
MIR543 affects OTUD1
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MIR543 decreases the amount of OTUD1. 1 / 1
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No evidence text available
MIR421 affects OTUD1
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MIR421 decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
MCM7 affects OTUD1
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1 |

No evidence text available
MCM5 affects OTUD1
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1 |

No evidence text available
MCM3 affects OTUD1
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1 |

No evidence text available
MAVS affects TRAF6
| 1
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
Lipopolysaccharides increases the amount of OTUD1. 1 / 1
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No evidence text available
Klk9 affects TRAF6
| 1
| 1

sparser
"Interestingly, we did not observe obvious co-localization between OTUD1 and the mitochondria during SeV infection ( xref ), which is also consistent with the observation that OTUD1 does not interact with MAVS, TRAF3, or TRAF6 in cells infected with SeV ( xref )."
K63 affects OTUD1
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OTUD1 binds IRF3 and K63. 1 / 1
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"As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63 linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity."
IRS4 affects OTUD1
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1 |

No evidence text available
IRF7 affects OTUD1
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1 |

No evidence text available
IRF3 affects K63, and OTUD1
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OTUD1 binds IRF3 and K63. 1 / 1
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"As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63 linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear translocation and transcriptional activity."
IP6K2 affects OTUD1
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No evidence text available
IGF2BP3 affects OTUD1
| 1
IGF2BP3 increases the amount of OTUD1. 1 / 1
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"In non-small cell lung cancer experiments, the overexpression of the cyclic RNA insulin-like growth factor 2 mRNA-binding protein 3 (circIGF2BP3) upregulates the expression of OTUD1 by stabilizing mRNA (98)."
IBA57 affects OTUD1
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1 |

No evidence text available
HSPA4 affects OTUD1
1 |
1 |

No evidence text available
HSP90AB1 affects OTUD1
1 |

No evidence text available
H3-5 affects OTUD1
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1 |

No evidence text available
Grape Seed Proanthocyanidins increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
GTF2I affects OTUD1
1 |
1 |

No evidence text available
FN1 affects VIM
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
| 1

sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
FARSA affects OTUD1
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1 |

No evidence text available
FADH2 affects OTUD1
| 1
FADH2 inhibits OTUD1. 1 / 1
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"The FDA-approved drug ibrutinib preferentially reduces the tumorigenicity of OTUD1 high ovarian cancer cells."
1 |
Enterolactone decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
ERBB2 affects OTUD1
| 1
| 1

sparser
"Furthermore, higher OTUD1 expression was significantly associated with low recurrence-free survival of HER2 + non-luminal subtype of breast cancer patients and EMT subtype of cervical cancer patients (Fig.  xref c, d)."
EIF3A affects OTUD1
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1 |

No evidence text available
EIF2S1 affects OTUD1
1 |
1 |

No evidence text available
EEF1G affects OTUD1
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1 |

No evidence text available
EEA1 affects OTUD1
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1 |

No evidence text available
Drugs, Chinese Herbal increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
Dnmt1 affects OTUD1
| 1
| 1

sparser
"Moreover, we observed that p53 showed better interaction with the UIM-lacking OTUD1 1-450 mutant than with WT OTUD1."
1 |
Dietary Fats increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
DNAJA1 affects OTUD1
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1 |

No evidence text available
DHRS7B affects OTUD1
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1 |

No evidence text available
DDE affects OTUD1
1 |
DDE decreases the amount of OTUD1. 1 / 1
1 |

No evidence text available
CUL3 affects OTUD1
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1 |

No evidence text available
CHCHD4 affects OTUD1
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1 |

No evidence text available
CDKN2AIP affects OTUD1
1 |

No evidence text available
CDK1 affects OTUD1
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1 |

No evidence text available
CDH2 affects VIM
| 1
CDH2 binds FN1, VIM, OTUD1, and CDH1. 1 / 1
| 1

sparser
"As expected, OTUD1 overexpression was associated with an increased expression level of the epithelial maker CDH1 and decreased expression levels of the mesenchymal markers CDH2 , FN1 , and VIM (Fig.  xref )."
CD274 affects OTUD1
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CD274 activates OTUD1. 1 / 1
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"CSN5 facilitates tumor growth by inhibiting the degradation of Snail241, ZEB1242, surviving243 and FOXM1244, whereas curcumin-induced CSN5 depletion decreases PD-L1 expression and enhances the anticancer efficacy of anti-CTLA4 drugs245.Tumor-suppressive DUB families, CYLD lysine 63 deubiquitinase (CYLD) in the USP family and OTU deubiquitinase 1 (OTUD1) in the OTU family, constitute the second type of DUBs."
CCT8 affects OTUD1
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1 |

No evidence text available
CCT3 affects OTUD1
1 |
1 |

No evidence text available
CAPRIN1 affects OTUD1
1 |
1 |

No evidence text available
CAD affects OTUD1
1 |
1 |

No evidence text available
C1QBP affects OTUD1
1 |
1 |

No evidence text available
BRD9 affects OTUD1
1 |
1 |

No evidence text available
BAG6 affects OTUD1
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1 |

No evidence text available
Aurora-A affects OTUD1
| 1
OTUD1 binds Aurora-A. 1 / 1
| 1

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"OTUD1, one of the final candidate DUBs for Aurora-A, bound to and deubiquitinated Aurora-A but its interaction with endogenous Aurora-A was much weaker than OTUD6A."
Acrylamide affects OTUD1
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Acrylamide increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
ATR inhibitor affects OTUD1
| 1
ATR inhibitor decreases the amount of OTUD1. 1 / 1
| 1

reach
"The ATR inhibitor VE-822 upregulates the expression level of the deubiquitinating enzyme OTUD1 to stabilize FHL1 expression through its OUT domain and inhibits the progression of lung adenocarcinoma."
ATP5PO affects OTUD1
1 |
1 |

No evidence text available
AKT3 affects OTUD1
1 |
1 |

No evidence text available
AKT2 affects OTUD1
1 |
1 |

No evidence text available
ACTG2 affects OTUD1
1 |
1 |

No evidence text available
ACBD3 affects OTUD1
1 |
1 |

No evidence text available
AAAS affects OTUD1
1 |
1 |

No evidence text available
293T affects PGAM5
| 1
OTUD1 binds PGAM5 and 293T. 1 / 1
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reach
"The initial confirmation of the interaction between OTUD1 and PGAM5 was conducted in 293T cells (Figure 6C-D)."
2-hydroxypropanoic acid increases the amount of OTUD1. 1 / 1
1 |

No evidence text available
1 |
17beta-estradiol increases the amount of OTUD1. 1 / 1
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No evidence text available
1,2-dichloroethane decreases the amount of OTUD1. 1 / 1
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No evidence text available
4,4'-sulfonyldiphenol decreases the amount of OTUD1. 1 / 1
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No evidence text available