IndraLab

Statements

OTUD4 is modified

9 | 67

OTUD4 is methylated.

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OTUD4 is methylated. 10 / 46

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"DNA methylation in AKR1B1, TM6SF1, TMEFF2, RASSF1, CCND2, HIN1, RARB, and TWIST1 genes were examined."

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"The high methylated HIN1 suppress itself expression in PCa, which exhibits tumor suppressor function and inhibits tumor cell growth, invasion by activation of AKT ( Krop et al., 2005 )."

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"A study has shown that parthenolide reversed the methylation of the HIN1 gene and induced re-expression in MCF-7 breast cancer cells."

37077808

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"This analysis showed that TGFβR2, CALCA , HIC1 , SOCS1, RARβ, COX2 , CDH1 , THBS1 , HIN1 , CDKN2B , UCHL1 , CCND2 , MT1G and DCC were frequently methylated in control samples, showing low specificity (Table xref )."

24359512

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"Among these genes, APC [ xref ], p16 [ xref ], RASSF1A [ xref ], DAPK1 [ xref ], CDH1 [ xref ], RARβ [ xref ], GSTP1 [ xref ], CyclinD2 [ xref ], HIN1 [ xref ] and TWIST [ xref ] are frequently methylated in breast cancer."

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"Although the evidence linking HIN1 levels to NB phenotype is unknown, our previous study indicated that methylation of HIN1 is associated with poor outcome in NB [ xref ]."

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"According to a study [ xref ], methylation of HIN1, TFPI-2, DACH1 and SOX17 can be used as markers for early detection of esophageal cancer."

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"Specifically, patients with ER+ or PR+ tumors had more frequent methylation of HIN1 and RASSF1A than those with ER- or PR- tumors."

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"Tamoxifen did not modulate methylation of CCND2, HIN1, CST6, or RAR-β2, but the mean difference for the sum of APC and RASSF1A methylation fractions between post-treatment and baseline samples was +7.1% for placebo subjects and −3.5% for tamoxifen subjects (P = 0.021)."

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"In tissue samples, 14-3-3-sigma, DAPK, CCND2, RASSF1A, CALCA, APC, HIN1, RARbeta2, TIG1, and GSTP1 methylation levels differed significantly among BCa, FB, and NT."

17549626

OTUD4 is phosphorylated.

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OTUD4 is phosphorylated. 10 / 20

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"Since OTUD4 appears to regulate MyD88-dependent signaling, we wished to determine whether phosphorylation of OTUD4 is altered during pathway activation."

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"This activity depends on the phosphorylation of OTUD4 near its catalytic domain ( xref ) as well as a putative UIM motif adjacent to the OTU domain ( xref )."

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"Detection of YFP-HIN1 in the wild-type (WT) or hai1-2 mutant background (where HIN1 may be more phosphorylated), after MG132 treatment found no evidence for decreased protein stability and in fact HIN1 accumulated to slightly higher level in the hai1-2 background even before MG132 treatment ()."

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"The phosphorylation of OTUD4, as well its putative UIM motif, are also important for MyD88 deubiquitination ( xref ), and consistently, these features are also critical for regulating IL-1β signaling ( xref )."

29395066

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"Among the DUBs, OTUD5 is the best understood example of activation by phosphorylation ( Huang et al., 2012 ), whereas OTUD4 phosphorylation markedly changes DUB chain-type specificity ( Zhao et al., 2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In addition, phosphorylation of OTUD4 confers K63 deubiquitinase activity, allowing it to deubiquitinate MyD88 and subsequently deactivate TLR-mediated NF-κB signaling [ xref ]."

32365080

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"Upon stimulation of murine bone-marrow-derived macrophages with heat-killed L. monocytogenes , phosphorylation of OTUD4 near its catalytic OTU domain activates the dormant K63-specific deubiquitinylat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

34016513

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"As OTUD4 is phosphorylated near its catalytic domain, it may function as a latent K63-specific deubiquitinase that regulates MyD88-dependent signaling [ 30 ]."

37739210

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"Here, we demonstrate that the deubiquitinase OTUD4, which nominally encodes a K48-specific deubiquitinase, is phosphorylated near its catalytic domain, activating a latent K63-specific deubiquitinase."

29395066

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"Furthermore, CKII-induced phosphorylation of OTUD4 promoted the preferential hydrolysis of the Ub chain changed from K48- to K63-linked chains, which plays an essential role in innate immune signalling ( xref )."

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OTUD4 is phosphorylated on S940. 9 / 9

9 |

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No evidence text available

16964243

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No evidence text available

20058876

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18767875

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No evidence text available

19664994

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No evidence text available

19651622

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19664995

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No evidence text available

19413330

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hprd

No evidence text available

18669648

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hprd

No evidence text available

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OTUD4 is dephosphorylated.

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OTUD4 is dephosphorylated. 1 / 1

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"HAI1 was even more effective than C.I.P. in dephosphorylation of full-length YFP-HIN1, as evidenced by loss of bands 1 and 2 on Phos-Tag gel ( xref )."

31611386

OTUD4 affects NT5E

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OTUD4 binds NT5E.

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NT5E binds OTUD4. 10 / 56

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"The heatmap presented in Supplemental Figure 10D displays the cross-correlation between the residues P264, I266, R273, and K274 that coordinate Z22, suggesting that Z22 binding to that specific pocket allosterically affects the conformation of the binding epitope, thus interfering with complex formation.To further understand the inhibitory effects of ST80 and Z22 on the regulation of CD73 stability, we performed a series of experiments to determine the optimal dose and treatment duration for ST80 and Z22 to disrupt the OTUD4/CD73 interaction."

38530357

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"The data together support a great potential of pharmacological targeting of the proteolytic interaction of OTUD4 and CD73 to mitigate tumor immune evasion and revive antitumor T cell immunity."

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"Pharmacological blockade of interaction of OTUD4 and CD73 promotes tumor immunogenicity and inhibits tumor progression in immune-cold breast cancer.."

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"To evaluate the importance of the physical interaction between OTUD4 and CD73 for tumor growth, we overexpressed both OTUD4 and CD73 (OTUD4 OE + CD73 ) or OTUD4 and CD73 with mutated interaction sites (OTUD4 OE + CD73 ) in EO771 cells."

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"ST80, a novel inhibitor that destroys the proteolytic interaction between OTUD4 and CD73, has the potential to enhance the efficacy of PD-L1 treatment in TNBC ( xref )."

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"However, we still observed the interaction between OTUD4 and CD73, although its proportion correlated with the decreased level of OTUD4 and CD73 proteins ( xref )."

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"Notably, OTUD4 overexpression heightened levels of membrane-bound CD73 in cancer cells."

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"In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic CD8 + T cell activities."

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"More importantly, we have developed a pharmacologic inhibitor, ST80 that is potent to specifically inhibit the physical interaction of OTUD4 and CD73 to promote ubiquitylation of CD73, thereby causing CD73 degradation and revival of CD8 T cell function."

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"These findings indicate a therapeutic value of pharmacologically targeting the proteolytic interaction of OTUD4 and CD73 to overcome the resistance of immune checkpoint inhibitors (e.g., anti-PD-L1 antibodies), especially in high CD73-expressing, immunologically suppressive TNBC."

38530357

OTUD4 deubiquitinates NT5E.

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OTUD4 deubiquitinates NT5E. 7 / 7

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"Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses."

38530357

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"Collectively, these results imply that TGF-β may enhance OTUD4 levels, contributing to the stabilization of CD73.To confirm the role of amino acids V300 and I301 in facilitating the TGF-β–mediated deubiquitylation of CD73 by OTUD4, Figure 4L shows that TGF-β treatment reduced the ubiquitylation level, which in turn stabilized the CD73 protein in MDA-MB-468-CD73 cells."

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38530357

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"Increased CD73 deubiquitylation by OTUD4 due to etiological factors enhances function for membrane-bound CD73, conferring tumor immune evasion."

38530357

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4 | 26 20

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"Our domain mapping results indicate that the TRAF domain of USP7 mediated the interaction between USP7 and OTUD4."

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"Based on our findings, we propose the development of a peptide or peptide-like inhibitors to disrupt the interaction between OTUD4 and USP7 as a potential antiviral strategy."

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"Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy."

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"Domain mapping experiments indicated that the N-terminal region of OTUD4 (1-425aa) interacted with USP7 ( xref )."

38215174

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"Notably, knockdown of USP7 in OTUD4-depleted cells could not further reduce KSHV progeny virion production ( xref ), suggesting that the OTUD4-USP7 axis plays a critical role in KSHV lytic reactivation."

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"Characterization of ALKBH3 interacting proteins show that USP7 and USP9x associate with another DUB OTU deubiquitinase 4 (OTUD4) to form a protein complex that deubiquitinates ALKBH3 [XREF_BIBR]."

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No evidence text available

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No evidence text available

25944111

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No evidence text available

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"Here, we developed a peptide, p8, which effectively disrupts the interaction between OTUD4 and USP7, leading to decreased abundance of the key viral transcription factor, RTA, and suppression of murine herpesvirus replication in vivo."

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OTUD4 affects MYD88

| 9 13

OTUD4 binds MYD88.

| 7 13

MYD88 binds OTUD4. 10 / 20

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"This suggests that SPARC can competitively bind to OTUD4, effectively obstructing the interaction between MYD88 and OTUD4."

39888301

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"BCA2 enhances the interaction between myeloid differentiation primary response protein 88 (MyD88) and Toll-like receptor 4 (TLR4) and inhibits the interaction of MyD88 with deubiquitinase OTUD4 in the LPS-mediated NF-κB signaling pathway."

38725852

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"Furthermore, BCA2 positively regulates LPS-induced NF-κB signaling activation by augmenting the interaction between MyD88 and TLR4 while hindering the interaction between MyD88 and OTUD4."

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"Furthermore, BCA2 positively regulates LPS-induced NF-κB signaling activation by augmenting the interaction between MyD88 and TLR4 while hindering the interaction between MyD88 and OTUD4."

38725852

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"BCA2 inhibits the interaction between MyD88 and OTUD4 and increases MyD88 ubiquitination."

38725852

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"We speculated that BCA2 prevents the binding of OTUD4 to MyD88."

38725852

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"Indeed, endogenous immunoprecipitation experiments following BCA2 knockout showed an increased interaction between MyD88 and OTUD4 (Fig. xref B)."

38725852

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"We speculated that BCA2 prevents the binding of OTUD4 to MyD88."

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OTUD4 deubiquitinates GSDME. 7 / 7

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"GSDME-dependent pyroptosis is a critical determinant of radiosensitivity in NPC, and is modulated by OTUD4 via deubiquitinating and stabilizing GSDME."

36411454

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"OTUD4 deubiquitinates and stabilizes GSDME."

36411454

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"In agreement with these findings, the overexpression of OTUD4 attenuated GSDME polyubiquitination (Fig. 5K)."

36411454

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"These results indicate that OTUD4 promotes the deubiquitination and stability of GSDME in NPC."

36411454

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"OTUD4 deubiquitinated and stabilized GSDME, thereby increasing GSDME-dependent pyroptosis and boosting radiosensitivity in NPC cells."

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"Additionally, OTUD4 deubiquitinates and stabilizes GSDME, resulting in increased levels of GSDME protein and radiation-induced pyroptosis, ultimately enhancing the radiosensitivity of NPC."

36411454

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"Furthermore, activated GSDME-induced pyroptosis enhances the radiosensitivity of colorectal cancer (89), and Di et al (90) revealed that the effect of GSDME on radiosensitivity is associated with GSDME deubiquitylation mediated by OTU deubiquitinase 4 in nasopharyngeal carcinoma."

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OTUD4 binds GSDME.

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GSDME binds OTUD4. 5 / 5

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"Interaction between OTUD4 and GSDME was confirmed by co-immunoprecipitation (co-IP) assays (Fig. 5D)."

36411454

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"In order to determine the regions that mediate the interaction between OTUD4 and GSDME, we made OTUD4 truncations and GSDME truncations (Fig. 5E)."

36411454

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36411454

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36411454

OTUD4 activates GSDME.

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OTUD4 activates GSDME. 5 / 5

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"Upregulation of OTUD4 significantly prolonged the half-life of endogenous GSDME, and silencing OTUD4 diminished the degradation half-life of GSDME in NPC cells (Fig. 5I and J)."

36411454

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"OTUD4 enhances radiosensitivity in NPC cells by promoting GSDME-dependent pyroptosis."

36411454

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"Upregulation of OTUD4 enhances radiosensitivity in NPC cells by promoting GSDME-dependent pyroptosis."

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"This suggests that SPARC can competitively bind to OTUD4, effectively obstructing the interaction between MYD88 and OTUD4."

39888301

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38725852

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"Furthermore, BCA2 positively regulates LPS-induced NF-κB signaling activation by augmenting the interaction between MyD88 and TLR4 while hindering the interaction between MyD88 and OTUD4."

38725852

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"Furthermore, BCA2 positively regulates LPS-induced NF-κB signaling activation by augmenting the interaction between MyD88 and TLR4 while hindering the interaction between MyD88 and OTUD4."

38725852

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"BCA2 inhibits the interaction between MyD88 and OTUD4 and increases MyD88 ubiquitination."

38725852

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"We speculated that BCA2 prevents the binding of OTUD4 to MyD88."

38725852

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"Indeed, endogenous immunoprecipitation experiments following BCA2 knockout showed an increased interaction between MyD88 and OTUD4 (Fig. xref B)."

38725852

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"We speculated that BCA2 prevents the binding of OTUD4 to MyD88."

38725852

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"BCA2 inhibits the interaction between MyD88 and OTUD4 and increases MyD88 ubiquitination."

38725852

OTUD4 affects SNAI1

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OTUD4 binds SNAI1.

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SNAI1 binds OTUD4. 10 / 11

1 | 2 8

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"Moreover, purified GST-OTUD4 could interact with recombinant His-Snail1 in vitro , indicating a direct interaction between OTUD4 and Snail1 ( Fig. 2 D)."

38040050

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"To further identify the region in Snail1 that associates with OTUD4, we generated two deletion mutants of Snail1 [ 21 ]: the N-terminal Snail1 [M1, amino acids (aa) 1–153], which contains the SNAG dom[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38040050

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No evidence text available

31911859

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"Furthermore, the interaction between OTUD4 and Snail1 was confirmed by immunofluorescence staining showing the co-localization of OTUD4 with Snail1 in the nucleus of MDA-MB-231 cells ( Fig. 2 F)."

38040050

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"Overall, our study establishes the OTUD4‐Snail1 axis as an important regulatory mechanism of BC metastasis and provides a rationale for potential therapeutic interventions in the treatment of TNBC."

38040050

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"The interaction of OTUD4 and Snail1 prompted us to examine a potential role for OTUD4 in the regulation of Snail1 stability in TNBC."

38040050

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"These results expanded our knowledge on the metastasis-promoting function of OTUD4 and provided preclinical evidence that targeting OTUD4-Snail1 axis might be a potential therapeutic strategy to conqu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Furthermore, the interaction between OTUD4 and Snail1 was confirmed by immunofluorescence staining showing the co-localization of OTUD4 with Snail1 in the nucleus of MDA-MB-231 cells ( Fig. 2 F)."

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"The interaction of OTUD4 and Snail1 prompted us to examine a potential role for OTUD4 in the regulation of Snail1 stability in TNBC."

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"We next confirmed the endogenous OTUD4-Snail1 interaction by co-immunoprecipitation assay in MDA-MB-231 cells ( Fig. 2 B and C)."

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OTUD4 deubiquitinates SNAI1.

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OTUD4 deubiquitinates SNAI1. 3 / 3

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"Meanwhile, the depletion of OTUD4 in MDA-MB-231 cells significantly increased Snail1 ubiquitination ( Fig. 4 C)."

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"Together, these results demonstrate that OTUD4 is a bona fide deubiquitinase targeting Snail1 for deubiquitination and stabilization.Since OTUD4 deubiquitinates and stabilizes Snail1, we next investig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"To sum up, our study demonstrated that OTUD4 deubiquitinates and stabilizes Snail1, thereby promoting metastasis of TNBC and targeting OTUD4 might be a potential therapeutic strategy in the treatment [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38040050

OTUD4 activates SNAI1.

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OTUD4 activates SNAI1. 2 / 2

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"Moreover, the depletion of OTUD4 in melanoma cells markedly inhibited Snail1 stability and Snail1-driven malignant phenotypes both in vitro and in vivo."

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38040050

OTUD4 increases the amount of SNAI1.

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OTUD4 increases the amount of SNAI1. 1 / 1

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"We found that the knockdown of OTUD4 in MDA-MB-231 and HCC1806 cells significantly decreased the protein level of Snail1 ( Fig. 3 A), but did not affect Snail1 mRNA levels ( Fig. 3 B)."

38040050

SPARC affects OTUD4

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SPARC binds OTUD4.

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SPARC binds OTUD4. 10 / 14

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"Besides, the direct interaction between SPARC and OTUD4 was evidenced in the colonic tissues of DSS‐induced colitis mice (Figure xref , Supporting Information)."

39888301

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"The direct interaction between SPARC and OTUD4 was verified by co‐IP (Figure xref )."

39888301

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"In order to better understand how SPARC‐OTUD4 interacts, we constructed a series of truncated fragments of SPARC and OTUD4 (Figure xref )."

39888301

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"These results suggest that SPARC directly interacted with OTUD4."

39888301

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"Mechanistically, it is elucidated that SPARC competitively binds to OTUD4 in conjunction with MYD88, facilitating the translocation of p65 from the cytoplasm to the nucleus and subsequent activation of the p65-MLCK/MLC2 pathway, thereby compromising barrier integrity."

39888301

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"The direct interaction between SPARC and OTUD4 was verified by co‐IP (Figure 4D)."

39888301

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"Besides, the direct interaction between SPARC and OTUD4 was evidenced in the colonic tissues of DSS‐induced colitis mice (Figure S5A, Supporting Information)."

39888301

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"This suggests that SPARC can competitively bind to OTUD4, effectively obstructing the interaction between MYD88 and OTUD4."

39888301

SPARC inhibits OTUD4.

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SPARC inhibits OTUD4. 1 / 1

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"These results suggest that overexpression of SPARC disrupts the effect of OTUD4 on K63‐poly‐Ub of MYD88."

39888301

OTUD4 affects KRT1

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OTUD4 binds KRT1.

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KRT1 binds OTUD4. 10 / 10

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"Overexpression of HA-OTUD4 interacted with FLAG-K-RTA in HEK293T cells, and endogenous OTUD4 also formed a complex with K-RTA when we induced KSHV lytic reactivation in both SLK."

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"These results confirmed that K-RTA interacts with OTUD4."

38215174

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"Interestingly, A C45A mutant that abrogates OTUD4 DUB activity [ xref , xref ] still interacted comparably with K-RTA, indicating that the DUB activity of OTUD4 is dispensable for K-RTA binding ( xref )."

38215174

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"Next, we mapped the regions that mediate the interaction between K-RTA and OTUD4."

38215174

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"Together, these data indicate that K-RTA interacts with OTUD4 and the C-terminal FRD motif of K-RTA and the N-terminal 1-425aa of OTUD4 mediate the interaction."

38215174

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"KSHV K-RTA interacts with OTUD4."

38215174

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"These data indicate that OTUD4 associates with K-RTA via the C-terminal FRD motif of K-RTA to facilitate KSHV lytic reactivation."

38215174

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"Since K-RTA plays a crucial role in KSHV reactivation and OTUD4 interacts with K-RTA, we hypothesized that OTUD4 may modulate K-RTA protein level to promote lytic reactivation."

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"Next, we mapped the regions that mediate the interaction between K-RTA and OTUD4."

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"In summary, we report that OTUD4 interacts with K-RTA and enhances K-RTA stability by promoting K-RTA deubiquitination."

38215174

OTUD4 increases the amount of KRT1.

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OTUD4 increases the amount of KRT1. 4 / 4

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"Moreover, OTUD4 (1-425aa) enhanced the protein level of K-RTA and the transcriptional activity of K-RTA, similar to the effects of WT OTUD4 (Figs 6H and S6D)."

38215174

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"To dissect how OTUD4 enhances K-RTA expression, we knocked down OTUD4 and then treated the cells with MG132 to block proteasomal degradation or Bafilomycin A1 to block lysosomal degradation."

38215174

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"Since K-RTA plays a crucial role in KSHV reactivation and OTUD4 interacts with K-RTA, we hypothesized that OTUD4 may modulate K-RTA protein level to promote lytic reactivation."

38215174

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"These data suggest that OTUD4 enhances K-RTA protein level by modulating the proteasomal degradation pathway."

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OTUD4 activates KRT1.

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OTUD4 activates KRT1. 1 / 1

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"Functionally, OTUD4 WT or the C45A mutant promoted K-RTA activity in reporter assays, however, the promoting effect was abrogated upon the depletion of USP7 (Fig 6D)."

38215174

OTUD4 affects SPARC

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SPARC binds OTUD4. 10 / 14

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"Besides, the direct interaction between SPARC and OTUD4 was evidenced in the colonic tissues of DSS‐induced colitis mice (Figure xref , Supporting Information)."

39888301

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"The direct interaction between SPARC and OTUD4 was verified by co‐IP (Figure xref )."

39888301

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"In order to better understand how SPARC‐OTUD4 interacts, we constructed a series of truncated fragments of SPARC and OTUD4 (Figure xref )."

39888301

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"These results suggest that SPARC directly interacted with OTUD4."

39888301

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"The direct interaction between SPARC and OTUD4 was verified by co‐IP (Figure 4D)."

39888301

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"Besides, the direct interaction between SPARC and OTUD4 was evidenced in the colonic tissues of DSS‐induced colitis mice (Figure S5A, Supporting Information)."

39888301

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"Consequently, we speculated that the interaction between SPARC and OTUD4 may inhibit the binding of MYD88 to OTUD4, thereby activating the MYD88‐dependent signal transduction."

39888301

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"This suggests that SPARC can competitively bind to OTUD4, effectively obstructing the interaction between MYD88 and OTUD4."

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OTUD4 affects ADSL

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OTUD4 decreases the amount of ADSL. 10 / 13

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"These data indicate that OTUD4 restricts the expression of AMPs through MyD88 after bacterial infection.It should be noted that the basal phosphorylation of TAK1, p65, and p38 was higher in Vil-Cre;Otud4 IECs than in Otud4 IECs (Fig. 5C)."

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"In in vitro generated intestinal organoids, the basal expression of AMPs was also higher in Vil-Cre;Otud4 organoids than in Otud4 organoids, which was impaired by ST2825 (Fig. 5D and E and Fig. S6D), indicating that OTUD4 constitutively interacts with MyD88 and inhibits MyD88-dependent signaling and expression of AMPs."

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"Here in this study, we have demonstrated that OTUD4 inhibits the expression of AMPs in Paneth cells and supports intestinal inflammation and bacterial infection through deubiquitinating MyD88."

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"Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) in Paneth cells restricts the expression of AMPs and thereby promotes experimental colitis and bacterial infection."

37193092

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"Knockout of OTUD4 promotes the expression of AMPs in intestinal organoids after stimulation with lipopolysaccharide (LPS) or peptidoglycan (PGN) and in the intestinal epithelial cells (IECs) of mice after DSS treatment or Salmonella typhimurium (S.t."

37193092

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"Mechanistically, knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of NF-kappaB and MAPKs to promote the expression of AMPs."

37193092

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"We further show that OTUD4 negatively regulates the expression of AMPs in IECs after DSS treatment or bacterial infection in a MyD88-dependent manner."

37193092

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"These results imply that the loss of OTUD4 in IECs does not inhibit the progression of colon cancer in the AOM/DSS and AOM/VP models.2.3 OTUD4 deficiency in IECs promotes the expression of AMPs and alters the microbiota after DSS treatment."

37193092

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"These data suggest that OTUD4 in IECs negatively regulates the expression of AMPs after DSS treatment.Because dysbiosis and alterations in the intestinal microbiota are associated with the progress of IBD and AMPs play an important role in restricting the invasion of the microbes in gut (Muniz et al., 2012), we collected feces from the Vil-Cre;Otud4 and the Otud4 mice which were given 2.5% DSS in drinking water for 0 or 5 days, and analyzed the microbial composition in the feces by 16S rRNA sequencing assays."

37193092

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"Results from qRT-PCR assays suggested that OTUD4 deficiency in Paneth cells promoted the expression of AMPs in the intestinal epithelium after DSS treatment (Fig. 4E), suggesting that OTUD4 in Paneth cells promotes intestinal inflammation.We next infected Def-Cre;Otud4 and Otud4 mice with S.t."

37193092

SNAI1 affects OTUD4

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"Moreover, purified GST-OTUD4 could interact with recombinant His-Snail1 in vitro , indicating a direct interaction between OTUD4 and Snail1 ( Fig. 2 D)."

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"Furthermore, the interaction between OTUD4 and Snail1 was confirmed by immunofluorescence staining showing the co-localization of OTUD4 with Snail1 in the nucleus of MDA-MB-231 cells ( Fig. 2 F)."

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"The interaction of OTUD4 and Snail1 prompted us to examine a potential role for OTUD4 in the regulation of Snail1 stability in TNBC."

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"Furthermore, the interaction between OTUD4 and Snail1 was confirmed by immunofluorescence staining showing the co-localization of OTUD4 with Snail1 in the nucleus of MDA-MB-231 cells ( Fig. 2 F)."

38040050

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"The interaction of OTUD4 and Snail1 prompted us to examine a potential role for OTUD4 in the regulation of Snail1 stability in TNBC."

38040050

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"We next confirmed the endogenous OTUD4-Snail1 interaction by co-immunoprecipitation assay in MDA-MB-231 cells ( Fig. 2 B and C)."

38040050

OTUD4 affects SERPINE1

2 | 4 5

OTUD4 binds SERPINE1.

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"Through protein profile screening, we found that OTUD4 may interact with protein PAI-1."

37726265

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"Further immunofluorescent stanning and co-immunoprecipitation proved that OTUD4 was associated with PAI-1 (Fig. xref )."

37726265

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"We further confirmed that OTUD4 interacted with PAI-1 for de-ubiquitination and inhibiting CSE induced PAI-1 degradation."

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"Our data indicated that OTUD4 is associated with PAI-1, a serine protease inhibitor (SERPIN), which is related to ubiquitin proteasome degradation in the regulating of cell death and was reported to promote angiogenesis and tumor cell survival by preventing apoptosis [ xref – xref ]."

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"Here, we found that OTUD4 interacts with PAI-1 and removes its K48-linked ubiquitination."

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OTUD4 decreases the amount of SERPINE1.

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OTUD4 decreases the amount of SERPINE1. 2 / 2

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"Reduced OTUD4 inhibited the expression of PAI-1 protein (Fig. 6A, left panel), while overexpression of OTUD4 partially reversed the protein level of PAI-1 in CSE treated BEAS-2b cells (Fig. 6A, right panel)."

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"In addition, ubiquitination assay showed that CSE can increase ubiquitination and degradation of PAI-1, while enhanced OTUD4 expression can decrease the ubiquitination level of PAI-1 induced by CSE (Fig. 7E)."

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OTUD4 increases the amount of SERPINE1.

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OTUD4 activates SERPINE1.

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"Results showed that OTUD4 knockdown promoted PAI-1 degradation, while OTUD4 overexpression slowdown the deduction of PAI-1 expression (Fig. 6D, E)."

37726265

OTUD4 affects Neoplasm Invasiveness

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OTUD4 activates Neoplasm Invasiveness.

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"Furthermore, MTT assay, colony formation assay, transwell assay and western blot assay results exhibited that overexpression of CDK1 could partially restore the phenotypes of GBM cell proliferation and invasion inhibition caused by OTUD4 knockdown, and the expressions of cell cycle and EMT-related proteins also changed correspondingly (Fig. 6E–H)."

38429268

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"Transwell assays demonstrated that OTUD4 knockdown in OE-100 cells significantly reduced lung cancer cell migration and invasion in vitro (Fig. S4C, D)."

40022086

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"Hence, we conclude that OTUD4 does affect the activation of the MAPK signaling pathway through the regulation of CDK1, and promote the proliferation and invasion ability of GBM cells."

38429268

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"Moreover, we provided in vitro and in vivo evidence that OTUD4 promotes the proliferation and invasion of GBM cells."

38429268

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"As shown in Fig. 1 A–D, the knockdown of OTUD4 by its specific shRNAs significantly reduced the migration and invasion abilities of MDA-MB-231 cells."

38040050

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"In addition, similar results were also observed in another TNBC cell line HCC1806 ( Fig. 1 A, E–G), which indicates that OTUD4 is pivotal for TNBC cell migration and invasion.To investigate underlying[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38040050

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"In addition, overexpression of OTUD4 notably promoted the proliferation and invasion of LN229 cells (Supplementary Fig. 2G–I, Supplementary Fig. 3E–G)."

38429268

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"OTUD4 promotes GBM cell proliferation and invasion."

38429268

OTUD4 inhibits Neoplasm Invasiveness.

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OTUD4 inhibits Neoplasm Invasiveness. 3 / 3

| 3

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"As further evidence that HIN-1 can influence invasive behavior, expression of HIN-1 markedly inhibited the invasion and migration of breast cancer cell lines in Boyden chamber assays."

| PMC

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"The expression of OTUD4 is significantly down-regulated in various solid tumor tissues, and the upregulation of OTUD4 impedes the proliferation, migration, and invasion of liver, breast and lung cancer cells by suppressing AKT pathway [32]."

36411454

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"It was reported that OTUD4 overexpression suppressed motility, invasion, and overproduction of breast, liver, and lung cancer in apoptosis/AKT signaling pathway, and so it could be used as a biomarker for many cancers ( 12 )."

36381277

OTUD4 affects MAVS

3 1 | 5 2

OTUD4 binds MAVS.

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OTUD4 binds MAVS. 5 / 5

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"Viral infection leads to the IRF3/7-dependent upregulation of OTUD4 which interacts with MAVS to remove K48-linked polyubiquitin chains, thereby maintaining MAVS stability and promoting innate antiviral signaling."

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"Viral infection causes the IRF3/7-dependent induction of OTUD4, which binds to MAVS to cleave K48-conjugated ubiquitin chains, stabilizing MAVS and activating antiviral innate immune responses [ xref ]."

36411454

OTUD4 deubiquitinates MAVS.

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OTUD4 deubiquitinates MAVS. 4 / 4

1 | 3

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"Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS"

30410068

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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]"

35675783

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"However, OTUD4 positively regulates IFN signaling and enhances host antiviral activities by deubiquitinating K48-Ub on MAVS (66)."

34707613

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"That study showed that OTUD4 deubiquitinates and stabilizes MAVS, thereby activating downstream signaling in the RIG-I like receptor RNA sensing pathway."

35516420

OTUD4 activates MAVS.

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OTUD4 activates MAVS. 2 / 2

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"OTUD4, a deubiquitinase, enhances MAVS mediated signaling by stabilizing MAVS and by eliminating K48 linked ubiquitins."

33462384

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"Upon viral infection, OTUD4 expression is induced to quickly stabilize MAVS, preparing it for timely response to infection (155)."

35795661

OTUD4 affects apoptotic process

| 10

OTUD4 inhibits apoptotic process.

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OTUD4 inhibits apoptotic process. 7 / 7

| 7

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"We further confirmed that increased OTUD4 prevented apoptosis in the lung tissue of CSE mouse model through TUNEL assay (Fig. 3E)."

37726265

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"In addition, we proved that knockdown of OTUD4 enhanced cell apoptosis in BEAS-2b through the TUNEL assay (Fig. 5D)."

37726265

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"Above results further demonstrated that OTUD4 silence promoted lung epithelial cell apoptosis.To verify whether OTUD4 could prevent the epithelia apoptosis, we overexpressed OTUD4 in BEAS-2b cells exposed to CSE."

37726265

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"Furthermore, TUNEL detection also confirmed that overexpression of OTUD4 can significantly reduce CSE induced lung cell apoptosis, while the apoptotic cells were significantly increased with tiplaxtinin treatment (Fig. 9G, H)."

37726265

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"In summary, the remarkable results of this study propose that overexpression of OTUD4 reduce cell apoptosis to protect against CSE treated lung epithelial cells and CSE mediated emphysematous model, which through PAI-1 activation."

37726265

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"Ovarian tumor family deubiquitinase 4 (OTUD4), a member of the OTU deubiquitinating enzyme, is implicated to decrease in cancer to regulate cell apoptosis."

37726265

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"Above all, this study added preliminary evidence that CSE induced OTUD4 reduction promoted epithelia apoptosis in COPD pathogenesis."

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OTUD4 activates apoptotic process.

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OTUD4 activates apoptotic process. 3 / 3

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"What’s more, loss of OTUD4 in Hela cells impaired stress granule formation and promoted apoptosis via activating caspase 3 [20]."

37726265

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"Overexpression of OTUD4 increases radiosensitivity of NSCLC cells exhibiting as impaired clonogenic formation ability, enhanced cell cycle arrest and increased cell apoptosis."

31011293

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"Expression of HIN-1 in synchronized cells inhibits cell cycle re-entry and the phosphorylation of the retinoblastoma protein (Rb), while in exponentially growing cells HIN-1 induces apoptosis without apparent cell cycle arrest or an effect on Rb phosphorylation."

| PMC

KRT1 affects OTUD4

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KRT1 binds OTUD4. 10 / 10

| 1 9

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"Overexpression of HA-OTUD4 interacted with FLAG-K-RTA in HEK293T cells, and endogenous OTUD4 also formed a complex with K-RTA when we induced KSHV lytic reactivation in both SLK."

38215174

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"These results confirmed that K-RTA interacts with OTUD4."

38215174

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"Next, we mapped the regions that mediate the interaction between K-RTA and OTUD4."

38215174

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"Together, these data indicate that K-RTA interacts with OTUD4 and the C-terminal FRD motif of K-RTA and the N-terminal 1-425aa of OTUD4 mediate the interaction."

38215174

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"KSHV K-RTA interacts with OTUD4."

38215174

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"These data indicate that OTUD4 associates with K-RTA via the C-terminal FRD motif of K-RTA to facilitate KSHV lytic reactivation."

38215174

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"Since K-RTA plays a crucial role in KSHV reactivation and OTUD4 interacts with K-RTA, we hypothesized that OTUD4 may modulate K-RTA protein level to promote lytic reactivation."

38215174

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"Next, we mapped the regions that mediate the interaction between K-RTA and OTUD4."

38215174

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"In summary, we report that OTUD4 interacts with K-RTA and enhances K-RTA stability by promoting K-RTA deubiquitination."

38215174

OTUD4 affects SETDB1

| 6 3

OTUD4 binds SETDB1.

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SETDB1 binds OTUD4. 6 / 6

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"However, in the absence of flag-tagged IRTKS, the interaction between OTUD4 and SETDB1 did not exist ( Fig. 4 D and E and S4E), suggesting that IRTKS acts as a scaffold protein to permit SETDB1 and OT[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

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"Co-IP assay using SK-Hep-1 cell lysates confirmed that IRTKS was essential in the interaction among IRTKS, OTUD4, and SETDB1, where in the absence of IRTKS, both SETDB1 and OTUD4 did not interact, but[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

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"Because the I-BAR domain mediates the interaction of both OTUD4 and SETDB1, we thus tested whether I-BAR deletion mutant can reverse the decreased H3K9me3 level and the increased SETDB1 ubiquitination[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"These data suggest that IRTKS may affect the protein accumulation of SETDB1 through OTUD4 deubiquitinase activity.Because the I-BAR domain mediates the interaction of both OTUD4 and SETDB1, we thus te[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

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"Interestingly, the deubiquitylation of OTUD4 on SETDB1 is dependent on IRTKS that recruits the two proteins, a deubiquitinase and its substrate, for their enzymatic reaction via the same I-BAR domain;[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

OTUD4 deubiquitinates SETDB1.

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"The ubiquitination experiments showed OTUD4 knockout increased SETDB1 ubiquitination ( Fig. S5A ), leading to its degradation ( Fig. 4 F)."

37739210

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"Conversely, the wild type (WT) OTUD4, but not OTUD4 C45A , reduced SETDB1 ubiquitination in liver cancer cells ( Fig. S5B ), even this OTUD4 C45A variant could still bind to IRTKS ( Fig. S5C ), which [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

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"These data indicate that OTUD4 can deubiquitinate SETDB1 in the presence of IRTKS, enhancing its stability.Ubiquitin conjugates with proteins via several residues including K48, which directs polyubiq[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

37739210

OTUD4 affects PFKFB3

1 | 8

OTUD4 binds PFKFB3.

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OTUD4 binds PFKFB3. 5 / 5

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"Consistently, immunofluorescence examination (Fig. 6f) and PLA assay (Fig. 6g) showed the enhanced interaction between OTUD4 and PFKFB3 in TGF-β1 treated NRCFs."

37162556

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"The binding affinity between PFKFB3 and OTUD4 was assayed by a Biacore T200 (GE Healthcare)."

37162556

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"Co-IP assay demonstrated that TGF-β1 treatment promoted the interaction of endogenous PFKFB3 and OTUD4 (Fig. 6d, e)."

37162556

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"Herein, we showed that TGF-β1 promoted the interaction of OTUD4 and PFKFB3."

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37162556

OTUD4 activates PFKFB3.

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OTUD4 activates PFKFB3. 4 / 4

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"Studies of post-myocardial infarction myocardial fibrosis revealed that OTU deubiquitinase 4 upregulated PFKFB3 to promote post-myocardial infarction cardiac fibrosis and that the inhibition of PFKFB3 helps ameliorate ischemia-induced cardiac fibrosis; therefore, the use of PFKFB3 inhibitors may provide a new therapeutic option for the treatment of post-myocardial infarction cardiac fibrosis (125)."

39301662

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"Deubiquitinase OTUD4 bonded to PFKFB3 and enhanced PFKFB3 stability via deubiquitylation upon TGF-β1 treatment."

37162556

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"OTUD4 promoted the stability of PFKFB3, leading to enhanced glycolysis and exacerbating cardiac fibrosis (Ref."

38525836

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"In addition, OTUD4 augments glycolysis by stabilizing glycolytic enzyme PFKFB3 in TGF-β1-treated cardiac fibroblasts and in cardiac fibroblasts of post-myocardial infarction mice [ 30 ]."

38040050

OTUD4 affects Neoplasms

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OTUD4 activates Neoplasms.

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OTUD4 activates Neoplasms. 6 / 6

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"The results suggest that CDH1 and HIN1 methylation heterogeneity may increase tumor metastasis."

34539742

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"We also found that OTUD4 OE in tumor cells enhanced a tumor-promoting M2-like phenotype in TAMs, usually defined by the expression of CD163 (Figure 6G)."

38530357

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"The data support a tumor-promoting role of the OTUD4/CD73 proteolytic axis in vivo.Previous studies have indicated that elevated levels of CD73 are often associated with an increase in immunosuppressive cell populations such as Tregs, MDSCs, and tumor-associated macrophages (TAMs) (32, 33)."

38530357

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38040050

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"In vivo assays substantiate that OTUD4 deletion, when combined with regorafenib, drastically reduces tumor proliferation, showcasing potent synergistic antitumor activity."

40338740

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"We further revealed a role of TGF-β signaling in orchestrating the OTUD4/CD73 proteolytic axis that promotes tumor progression."

38530357

OTUD4 inhibits Neoplasms.

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OTUD4 inhibits Neoplasms. 3 / 3

| 3

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"Thus, the potential involvements of these substrates of OTUD4 besides Snail1 in metastasis of TNBC and other malignant cancers need to be further investigated.Our study demonstrates that targeting OTU[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

38040050

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"OTUD4-mediated stabilization of CD73 suppressed cytotoxic CD8 T cell function, thereby facilitating tumor immune destruction."

38747288

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"They found that the expression level of the tumor suppressors HIN1 and CDH1 were elevated, and the methylation level of death-associated protein kinase 1 (DAPK-1), a breast tumorigenic gene, was decreased."

37391844

OTUD4 affects FGFR1

| 6 3

OTUD4 binds FGFR1.

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"OTUD4 interacts with FGFR1 and stabilizes FGFR1 by deubiquitination."

38429268

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"On the other hand, OTUD4 binds to fibroblast growth factor receptor 1 (FGFR1) and reduces FGFR1’s K6 and K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing the activation of the downstream MAPK signaling pathway."

38429268

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"OTUD4 interacts with FGFR1 and stabilizes FGFR1 by deubiquitination."

38429268

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"Co-IP and PLA assays found that OTUD4 interacts with FGFR1(Fig. xref , Supplementary Fig. xref )."

38429268

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"On the other hand, OTUD4 binds to fibroblast growth factor receptor 1 (FGFR1) and reduces FGFR1's K6 and K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing the activation of the downstream MAPK signaling pathway."

38429268

OTUD4 activates FGFR1.

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"CHX assay found that OTUD4 overexpression prolongs the half-life of FGFR1 (Fig. 5E, Supplementary Fig. 6H)."

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ICP0 ubiquitinates OTUD4. 5 / 5

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"To examine whether VIM and OTUD4 were ubiquitinated by ICP0, we co-transfected ubiquitin, VIM or OTUD4, and ICP0 or its control (empty vector or ring finger mutant) into Neuro-2a cells before immunoprecipitation of VIM and OTUD4 and analysis of ubiquitination levels by Western blots."

35516420

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"OTUD4 and VIM Could Be Ubiquitinated by ICP0."

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| 8

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"In nasopharyngeal carcinoma (NPC), Zhao C et al. reported that OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity of NPC cells by promoting their pyroptosis 116."

38323315

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"Ovarian tumor family deubiquitinase 4 (OTUD4) was found to stabilize GSDME through deubiquitination, enhance tumor cell pyroptosis and increase radiosensitivity."

40201182

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"Ovarian tumour family deubiquitinase 4 (OTUD4) can enhance radiosensitivity in nasopharyngeal carcinoma cells by positively regulating pyroptosis via GSDME deubiquitination 117."

37781519

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"Ovarian tumor family deubiquitinase 4 (OTUD4) enhanced radiosensitivity of nasopharyngeal carcinoma by promoting pyroptosis through deubiquitination and stabilization of GSDME (24)."

40201182

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"Upregulation of OTUD4 enhances radiosensitivity in NPC cells by promoting GSDME-dependent pyroptosis."

36411454

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"OTUD4 enhances radiosensitivity in NPC cells by promoting GSDME-dependent pyroptosis."

36411454

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"Mechanistically, OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity of NPC cells by promoting pyroptosis."

36411454

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"In addition, we demonstrated that OTUD4 deubiquitinated and stabilized GSDME, enhancing radiosensitivity in NPC by promoting GSDME-dependent pyroptosis."

36411454

OTUD4 affects CDK1

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OTUD4 binds CDK1.

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"Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination."

38429268

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"Moreover, the proximity ligation assay (PLA) assay also corroborated a direct in situ interaction of OTUD4 with CDK1(Fig. xref )."

38429268

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"Mechanistically, on the one hand, we demonstrated a direct protein interaction between OTUD4 (181-300aa) and CDK1, and OTUD4 regulates the stability of CDK1 by deubiquitination."

38429268

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"Mechanistically, on the one hand, we demonstrated a direct protein interaction between OTUD4 (181-300aa) and CDK1, and OTUD4 regulates the stability of CDK1 by deubiquitination."

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OTUD4 binds CDK1 and K11. 1 / 1

| 1

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"Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination."

38429268

OTUD4 inhibits CDK1.

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OTUD4 inhibits CDK1. 2 / 2

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"MG132 (an inhibitor of the ubiquitin-proteasome pathway) dramatically blocks the downregulation of CDK1 caused by OTUD4 knockdown (Fig. 4A), suggesting that OTUD4 protects CDK1 from proteasome-dependent degradation."

38429268

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"Next, our results corroborated that FGFR1 interference exacerbated the CDK1 downregulation caused by OTUD4 knockdown, and FGFR1 may maintain CDK1 protein stability by stabilizing the CDK1-cyclinB1 complex (Fig. 5J, K)."

38429268

OTUD4 deubiquitinates CDK1.

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| 1

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"In this context, OTUD4 plays a crucial role in cell proliferation, invasion, and clonogenic capacity by deubiquitinating CDK1 and activating the MAPK signaling pathway (15)."

38747288

SPINT1 affects OTUD4

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SPINT1 dephosphorylates OTUD4.

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"Second, HIN1–HAI1 interaction, as well as HAI1 dephosphorylation of HIN1, provides a link between stress signaling and pre-mRNA splicing."

31611386

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"To determine whether HAI1 could dephosphorylate HIN1, YFP-HIN1 was immunoprecipitated, incubated with recombinant HAI1 or nonspecific phosphatase (C.I.P."

31611386

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"In contrast, HAI1 could not fully dephosphorylate the N-terminal HIN1 truncation (bands 3 and 4 on Phostag gel and band 5 on SDS/PAGE; Fig. 1E)."

31611386

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"However, it is unlikely that this occurs via effects on HIN1 RNA binding since this occurred at the N-terminal region, while HAI1 interacted with and dephosphorylated the C-terminal portion of HIN1."

31611386

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"To determine whether HAI1 could dephosphorylate HIN1, YFP-HIN1 was immunoprecipitated, incubated with recombinant HAI1 or nonspecific phosphatase (C.I.P.), and analyzed on Phos-Tag gels."

31611386

SPINT1 binds OTUD4.

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SPINT1 binds OTUD4. 2 / 2

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"HAI1 interaction with full-length HIN1 was not detected in yeast 2-hybrid assays, possibly because nuclei acid binding activity of the N-terminal domain interfered with the assay.Coimmunoprecipitation confirmed HAI1–HIN1 interaction in planta and indicated that there was more extensive interaction in stress-treated plants (Fig. 1B)."

31611386

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"Interestingly, HIN1 interaction with HAI1, HAI2, or HAI3, but not the HAB1 or ABI1 interaction, was sometimes observed as speckles within the nucleus (Fig. 1D and SI Appendix, Fig. S2A)."

31611386

SERPINE1 affects OTUD4

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"Through protein profile screening, we found that OTUD4 may interact with protein PAI-1."

37726265

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"Further immunofluorescent stanning and co-immunoprecipitation proved that OTUD4 was associated with PAI-1 (Fig. xref )."

37726265

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"We further confirmed that OTUD4 interacted with PAI-1 for de-ubiquitination and inhibiting CSE induced PAI-1 degradation."

37726265

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37726265

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"Here, we found that OTUD4 interacts with PAI-1 and removes its K48-linked ubiquitination."

37726265

OTUD4 affects cell population proliferation

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OTUD4 activates cell population proliferation.

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OTUD4 activates cell population proliferation. 5 / 5

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"In vivo assays substantiate that OTUD4 deletion, when combined with regorafenib, drastically reduces tumor proliferation, showcasing potent synergistic antitumor activity."

40338740

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"Hence, we conclude that OTUD4 does affect the activation of the MAPK signaling pathway through the regulation of CDK1, and promote the proliferation and invasion ability of GBM cells."

38429268

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"Moreover, we provided in vitro and in vivo evidence that OTUD4 promotes the proliferation and invasion of GBM cells."

38429268

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"OTUD4 promotes GBM cell proliferation and invasion."

38429268

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"In addition, overexpression of OTUD4 notably promoted the proliferation and invasion of LN229 cells (Supplementary Fig. 2G–I, Supplementary Fig. 3E–G)."

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OTUD4 inhibits cell population proliferation.

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"As a member of the OTU family, OTUD4 has also been shown to affect cancer progression, for example, on the one hand, OTUD4 acts as an oncogene to facilitate the metastasis of triple-negative breast cancer [38] and melanoma [39]; on the other hand, OTUD4 acts as a tumor suppressor gene to inhibit the proliferation of liver cancer and non-small cell lung cancer, and regulate the radiosensitivity of nasopharyngeal carcinoma [40]."

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OTUD4 affects XPC

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OTUD4 binds XPC.

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XPC binds OTUD4. 4 / 4

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"We validated the XPC-OTUD4 interaction by co-IP and demonstrated that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by removing the ubiquitin moiety."

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"In addition, we have validated the OTUD4–XPC interaction in Human cells."

24366067

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"We found that XPC and OTUD4 interact directly in a co-immunoprecipitation experiment ( xref )."

24366067

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"Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety."

24366067

OTUD4 deubiquitinates XPC.

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OTUD4 deubiquitinates XPC. 3 / 3

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"We speculate that deubiquitination of XPC by OTUD4 could be responsible for the removal of XPC from damage sites, possibly leading to XPC recycling."

24366067

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"It is not known whether OTUD4 works independently or cooperatively with USP7 to deubiquitinate XPC."

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"Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety."

24366067

OTUD4 affects GST

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OTUD4 binds GST. 7 / 7

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"GST-OTUD4 protein was purified using Pierce Glutathione agarose (Thermo Scientific, Maryland, USA)."

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"The his-tagged SETDB1 and flag-tagged IRTKS were purified and then added to GST beads binding GST-tagged OTUD4, the result showed that the amount of SETDB1 pulled down by the GST-OTUD4 was obviously i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Purified GST, full-length, truncated GST-IRTKS, GST-OTUD4, and GST-SETDB1 constructs bound to glutathione-Sepharose 4B beads (30 μl GE) was incubated with His-tag protein."

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"GST–OTUD4 or GST protein alone, as a control, were coupled to glutathione–Sepharose beads and incubated with biotinylated RNA or without RNA."

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"Moreover, purified GST-OTUD4 could interact with recombinant His-Snail1 in vitro , indicating a direct interaction between OTUD4 and Snail1 ( Fig. 2 D)."

38040050

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"The fluorescence intensity in the presence of biotinylated RNA was more than 10-fold higher for GST–OTUD4 compared to the GST control, indicating that OTUD4 was able to bind RNA under these conditions ( xref B)."

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"Recombinant GST-OTUD4 and pET28a-Snail1 proteins were expressed in Escherichia coli strain BL21."

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SETDB1 affects OTUD4

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SETDB1 binds OTUD4. 6 / 6

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OTUD4 affects UBL7

2 | 4

OTUD4 binds UBL7.

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UBL7 binds OTUD4. 4 / 4

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"This result suggests that the effect of UBL7 on the K48-linked ubiquitination of MAVS is not directly through OTUD4.We further determined the role of interaction between OTUD4 and UBL7."

36943869

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"Moreover, an interaction between exogenous myc-UBL7 and flag-TRIM21 or flag-OTUD4 was observed by coIP ( Figure 5 B)."

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OTUD4 increases the amount of UBL7.

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"Therefore, as a DUB of UBL7, OTUD4 increased the accumulation of UBL7 by removing its K11-linked ubiquitination and enhanced the promoting effect of UBL7 on MAVS-TRIM21 interaction during viral infect[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In addition, OTUD4 overexpression in 293 T cells promoted the accumulation of UBL7 protein, while knockdown of OTUD4 reduced the protein level of UBL7 ( Figure S2 C)."

36943869

OTUD4 affects MYCBP

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OTUD4 binds MYCBP. 6 / 6

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"Last, we detect interactions between OTUD4, the close human homolog of Drosophila OTU, and MYCBP in human cell lines."

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"Regardless, physical interactions between OTUD4 and MYCBP reveal that the association of these proteins has been conserved across evolution."

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"Regardless, physical interactions between OTUD4 and MYCBP reveal that the association of these proteins has been conserved across evolution."

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33961781

OTUD4 affects Deubiquitinase

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OTUD4 activates Deubiquitinase. 6 / 6

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"The DUB-deficient mutant C45A also effectively rescued KSHV lytic reactivation (Fig 2F and 2G), confirming that OTUD4 promotes KSHV lytic reactivation independent of its DUB activity."

38215174

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"Collectively, these data indicate that OTUD4 promotes KSHV lytic reactivation independent of its DUB activity."

38215174

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"However, studies reported that the deubiquitase recruitment domain (DRD, 181–550aa) of OTUD4 interacts with and deubiquitinates ALKBH3 [41, 42], intrinsically disordered regions (IDRs, such as 885–1114aa) of OTUD4 interacts with RNA [43], the ubiquitin interaction motif (UIM, 271–300aa) of OTUD4 promotes its DUB activity against MyD88 [10]."

38429268

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"Phosphorylation of OTUD4 activates its K63-specific DUB activity [10]."

38429268

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"Based on these, we speculated that 301–550aa of OTUD4 is the catalytic domain for deubiquitination of CDK1, and 181–300aa of OTUD4 might promote the DUB activity of OTUD4 on CDK1 by enhancing their interaction ability.On the one hand, in order to identify which type of polyubiquitin modifications on CDK1 was affected by OTUD4, we performed a thorough deubiquitylation assay."

38429268

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"OTUD4 promotes KSHV lytic replication independent of its DUB activity."

38215174

MYCBP affects OTUD4

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OTUD4 binds MYCBP. 6 / 6

3 | 1 2

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"Last, we detect interactions between OTUD4, the close human homolog of Drosophila OTU, and MYCBP in human cell lines."

40215271

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"Regardless, physical interactions between OTUD4 and MYCBP reveal that the association of these proteins has been conserved across evolution."

40215271

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No evidence text available

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"Regardless, physical interactions between OTUD4 and MYCBP reveal that the association of these proteins has been conserved across evolution."

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No evidence text available

33961781

Harpin affects OTUD4

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Harpin activates OTUD4. 5 / 5

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"This showed that the harpin induced 1 (HIN1) gene is responsive to Spm."

15316293

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"Moreover, the NHL6 and the LRR receptor kinases may be defence-related because the former is induced in response to SA and similar to non-race-specific disease resistance NDR1 and harpin-induced HIN1 genes, and the latter are involved in defence and/or development ."

38424101

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"In the case of AWR5, its overexpression in tobacco species triggers a rapid increase in the expression of harpin-induced 1 (HIN1), which is an HR-specific marker."

| PMC

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"The higher expression of HR marker genes, harpin-induced 1 (Hin1) and hypersensitivity-related (Hsr203JI), supported the role of C1 and Rep in HR response in plants."

35960462

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"In contrast to activation by beta-megaspermin, harpin (Psph)-induced activation of the 48-kD salicylic acid responsive mitogen activated protein kinase (MAPK) and HIN1 transcript accumulation were independent of extracellular calcium."

11340183

USP9X affects OTUD4

3 | 1 1

OTUD4 binds USP9X. 5 / 5

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"Characterization of ALKBH3 interacting proteins show that USP7 and USP9x associate with another DUB OTU deubiquitinase 4 (OTUD4) to form a protein complex that deubiquitinates ALKBH3 [XREF_BIBR]."

30831436

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"If indeed OTUD4-bound USP9X can affect TβR deubiquitination, it may explain both the catalytic and non-catalytic functions of OTUD4 in TGFβ regulation."

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UBC affects OTUD4

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PFKFB3 affects OTUD4

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OTUD4 binds PFKFB3. 5 / 5

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"Consistently, immunofluorescence examination (Fig. 6f) and PLA assay (Fig. 6g) showed the enhanced interaction between OTUD4 and PFKFB3 in TGF-β1 treated NRCFs."

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"The binding affinity between PFKFB3 and OTUD4 was assayed by a Biacore T200 (GE Healthcare)."

37162556

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"Co-IP assay demonstrated that TGF-β1 treatment promoted the interaction of endogenous PFKFB3 and OTUD4 (Fig. 6d, e)."

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"Herein, we showed that TGF-β1 promoted the interaction of OTUD4 and PFKFB3."

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37162556

OTUD4 affects USP9X

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OTUD4 binds USP9X. 5 / 5

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"Characterization of ALKBH3 interacting proteins show that USP7 and USP9x associate with another DUB OTU deubiquitinase 4 (OTUD4) to form a protein complex that deubiquitinates ALKBH3 [XREF_BIBR]."

30831436

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"If indeed OTUD4-bound USP9X can affect TβR deubiquitination, it may explain both the catalytic and non-catalytic functions of OTUD4 in TGFβ regulation."

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OTUD4 affects UBC

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OTUD4 affects TGFB

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OTUD4 activates TGFB. 5 / 5

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"OTUD4 enhances TGFbeta signalling through regulation of the TGFbeta receptor complex ."

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"Previously, OTUD4 was reported to regulate the TGFβ receptor complex and enhance TGFβ signaling, which could stimulate tumor cells to undergo EMT and promote CSC invasion and metastasis [ 26–29 ]."

38040050

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eidos

"Specifically , we find that OTUD4 enhances TGFbeta signalling by promoting the membrane presence of TGFbeta receptor I. Furthermore , we demonstrate that OTUD4 inactivates the TGFbeta negative regulator SMURF2 suggesting that OTUD4 regulates multiple nodes of the TGFbeta pathway to enhance TGFbeta activity ."

32973272

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"OTUD4 enhances TGFbeta signalling through regulation of the TGFbeta receptor complex."

32973272

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"OTUD4 in the TGF-β signalling pathway enhances overall TGF-β activity through a positive feedback loop."

37625521

OTUD4 affects MHV68

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OTUD4 activates MHV68. 5 / 5

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"Notably, the DUB-deficient mutants (C45A and ΔDUB) also effectively rescued MHV68 replication (Fig 4E), indicating that OTUD4 promotes MHV68 lytic replication independently of its DUB activity.To investigate OTUD4’s role in MHV68 replication in vivo, we administered tamoxifen to Otud4 Cre-ERT2 and Otud4 Cre-ERT2 mice to induce OTUD4 knockout, followed by MHV68 infection via intranasal inoculation."

40208866

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"Our data indicate that knockout of OTUD4 in mice greatly impairs the replication of MHV68, a murine herpesvirus closely related to KSHV, thereby validating the critical role of OTUD4 in MHV68 replication in vivo."

40208866

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"OTUD4 deficiency impairs MHV68 replication."

40208866

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"Next, we asked whether OTUD4 also promotes the replication of MHV68, a murine herpesvirus that is genetically and biologically relevant to KSHV."

40208866

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"Knockdown of OTUD4 in NIH3T3 cells significantly impaired MHV68 lytic replication, as indicated by the decreased GFP intensity (S4A and S4B Fig)."

40208866

OTUD4 affects ALKBH3

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OTUD4 binds ALKBH3.

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25944111

OTUD4 deubiquitinates ALKBH3.

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OTUD4 deubiquitinates ALKBH3. 1 / 1

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"Besides USP11, OTUD4 is another USP7 partner that deubiquitinates DNA demethylases ALKBH2 and ALKBH3 [118]."

33991872

OTUD4 affects ALDOA

| 4 1

OTUD4 binds ALDOA.

| 2 1

ALDOA binds OTUD4. 3 / 3

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"We further investigated whether Mir100hg regulates the interaction between ALDOA and OTUD4."

40022086

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"This finding adds to the growing body of evidence supporting the importance of ceRNA networks in cancer progression.The second mechanism involves post-translational modification, where Mir100hg acts as a molecular scaffold to facilitate the interaction between ALDOA and the deubiquitinating enzyme OTUD4, preventing ALDOA ubiquitination and increasing its protein abundance."

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"We further investigated whether Mir100hg regulates the interaction between ALDOA and OTUD4."

40022086

OTUD4 deubiquitinates ALDOA.

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OTUD4 leads to the deubiquitination of ALDOA. 2 / 2

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"Thus, we hypothesized that OTUD4 may promote ALDOA deubiquitination."

40022086

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"Silencing OTUD4 in OE-Mir100hg cells significantly increased ALDOA ubiquitination (Fig. 4G; Fig. S4B)."

40022086

OTUD4 affects AKT

| 5

OTUD4 inhibits AKT.

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OTUD4 inhibits AKT. 3 / 3

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"Akt pathway activity repressed by HIN-1 was enhanced in HIF-2alpha-deficient human NSCLC cells and xenografts [XREF_BIBR]."

22871047

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"Expression of HIN-1 also inhibits Akt mediated retention of p27 in the cytoplasm."

| PMC

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36411454

OTUD4 activates AKT.

| 2

OTUD4 activates AKT. 2 / 2

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"AKT signaling pathway activated by HIN-1 methylation in non small cell lung cancer."

25312249

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"AKT signaling pathway activated by HIN-1 methylation in non small cell lung cancer."

22095135

MAVS affects OTUD4

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GSDME affects OTUD4

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"Interaction between OTUD4 and GSDME was confirmed by co-immunoprecipitation (co-IP) assays (Fig. 5D)."

36411454

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"In order to determine the regions that mediate the interaction between OTUD4 and GSDME, we made OTUD4 truncations and GSDME truncations (Fig. 5E)."

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FGFR1 affects OTUD4

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OTUD4 binds FGFR1. 5 / 5

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"OTUD4 interacts with FGFR1 and stabilizes FGFR1 by deubiquitination."

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"OTUD4 interacts with FGFR1 and stabilizes FGFR1 by deubiquitination."

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"Co-IP and PLA assays found that OTUD4 interacts with FGFR1(Fig. xref , Supplementary Fig. xref )."

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CDK1 affects OTUD4

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OTUD4 binds CDK1. 4 / 4

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"Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination."

38429268

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"Moreover, the proximity ligation assay (PLA) assay also corroborated a direct in situ interaction of OTUD4 with CDK1(Fig. xref )."

38429268

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"Mechanistically, on the one hand, we demonstrated a direct protein interaction between OTUD4 (181-300aa) and CDK1, and OTUD4 regulates the stability of CDK1 by deubiquitination."

38429268

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"Mechanistically, on the one hand, we demonstrated a direct protein interaction between OTUD4 (181-300aa) and CDK1, and OTUD4 regulates the stability of CDK1 by deubiquitination."

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OTUD4 binds CDK1 and K11. 1 / 1

| 1

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"Mechanism studies showed that, on the one hand, OTUD4 directly interacts with cyclin-dependent kinase 1 (CDK1) and stabilizes CDK1 by removing its K11, K29, and K33-linked polyubiquitination."

38429268

Bisphenol A affects OTUD4

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XPC affects OTUD4

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XPC binds OTUD4. 4 / 4

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"In addition, we have validated the OTUD4–XPC interaction in Human cells."

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"We found that XPC and OTUD4 interact directly in a co-immunoprecipitation experiment ( xref )."

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UBL7 affects OTUD4

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"This result suggests that the effect of UBL7 on the K48-linked ubiquitination of MAVS is not directly through OTUD4.We further determined the role of interaction between OTUD4 and UBL7."

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OTUD4 inhibits ferroptosis. 2 / 2

| 1 1

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"OTUD4 inhibits ferroptosis by stabilizing GPX4 and suppressing autophagic degradation to promote tumor progression."

40338740

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"OTUD4 inhibits ferroptosis by stabilizing GPX4 and suppressing autophagic degradation to promote tumor progression."

40338740

OTUD4 activates ferroptosis.

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OTUD4 activates ferroptosis. 2 / 2

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"We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death."

38553613

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"Mechanistically, circFOXP1-231aa directly interacted with OTUD4, which regulates NCOA4 protein stability via deubiquitination modification, and thereby enhances ferroptosis of ICC cells."

38945202

OTUD4 affects RNF216

| 2 2

OTUD4 binds RNF216.

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RNF216 binds OTUD4. 3 / 3

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"Mutations in the ubiquitin ligase RNF216 and the deubiquitianse OTUD4 also associate with GHS."

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OTUD4 inhibits OTUD4. 1 / 1

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39888301

OTUD4 decreases the amount of OTUD4.

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Methylated OTUD4 decreases the amount of OTUD4. 1 / 1

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"We also identified that methylation of HIN-1 downregulated the expression of HIN-1 in OCCA cell lines and cancerous tissues according to RT-PCR, Western blot, and IHC analyses."

22871047

OTUD4 affects Bacterial Infections

| 4

OTUD4 activates Bacterial Infections.

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OTUD4 activates Bacterial Infections. 3 / 3

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"The bacterial counts in feces, cecum, liver and spleen of the Vil-Cre;Otud4 mice were also significantly reduced compared to Otud4 mice (Fig. 3E), indicating that OTUD4 promotes bacterial infection in vivo."

37193092

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OTUD4 binds BNS1. 2 / 2

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"The interaction of OTUD4 and BNS1 was then confirmed using co-IPs (Figure 4C)."

38089580

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"In addition, we found that CypA did not interact with OTUD4 (Figure S3A) or affect the interaction between BNS1 and OTUD4 (Figure S3B)."

38089580

ALKBH3 affects OTUD4

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Rep affects OTUD4

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Rep binds OTUD4. 3 / 3

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WBP2NL affects OTUD4

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USP7-TRAF affects OTUD4

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OTUD4 binds USP7-TRAF. 3 / 3

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"Moreover, while p8 effectively blocked the interaction between OTUD4 and USP7-TRAF, the p8m mutant (S8A) failed to do so (Fig 2F)."

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"Additionally, p2 failed to disrupt the interaction between USP7-TRAF and OTUD4 (S2A Fig)."

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"Specifically, mutation of Asp164 or Trp165 in USP7-TRAF to Alanine significantly reduced OTUD4 binding in GST pull-down assays, confirming that Asp164 and Trp165 are critical for the interaction between OTUD4 and USP7-TRAF (Fig 2E)."

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TRIM21 affects OTUD4

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TRIM21 binds OTUD4. 3 / 3

| 2 1

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"After the affinity purification by UBL7, mass spectrum results showed that UBL7 interacted with TRIM21 and OTUD4 ( Figure 5 A)."

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"Moreover, an interaction between exogenous myc-UBL7 and flag-TRIM21 or flag-OTUD4 was observed by coIP ( Figure 5 B)."

36943869

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"To comprehensively address the mechanism by which the interplay of TRIM21-mediated ubiquitylation and OTUD4-guided deubiquitylation regulates CD73 proteolysis, we conducted structural modeling of the interaction between CD73, TRIM21, and OTUD4 by integrated use of experimental data and docking simulations followed by experimental validation."

38530357

TRAF6 affects OTUD4

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"Last, further studies are necessary to illustrate the mechanism by which OTUD4 interacts with TRAF6."

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"To investigate the relationship between OTUD4 and TRAF6, we first verified that OTUD4 interacts with TRAF6 by using coimmunoprecipitation ( Fig. 2 A)."

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"In this study, we found that OTUD4 can physically interacts with TRAF6."

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TRAF1 affects OTUD4

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SMN2 affects OTUD4

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"Because OTUD4 interacted with SMN1 in co-IPs and SMN1 has been well characterized in neuronal RNP granules ( xref ; xref ), we co-expressed mOrange2–OTUD4 with neonGreen–SMN1 in hippocampal neurons for live-cell imaging."

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RNF216 affects OTUD4

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"Mutations in the ubiquitin ligase RNF216 and the deubiquitianse OTUD4 also associate with GHS."

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"Indeed, the phenotype in the index pedigree appears to have been caused by the interaction of hypomorphic mutations in RNF216 and OTUD4 ."

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"This possibility is bolstered by the observation of epistatic interactions between RNF216 and OTUD4, with simultaneous knockdown of both genes resulting in more severe phenotypes."

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RC3H1 affects OTUD4

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PPIA affects OTUD4

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"CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination to stabilize BNS1 by upregulating OTUD4 expression."

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"CypA promotes OTUD4-mediated K48-linked BNS1 deubiquitination."

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"Therefore, CypA might enhance OTUD4-mediated K48-linked deubiquitination of BNS1 by upregulating OTUD4 expression."

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OTUD4

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"Additionally, OTUD4 translocates into the nucleus after KSHV lytic reactivation and co-localizes with K-RTA."

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"Additionally, OTUD4 translocates into the nucleus after KSHV lytic reactivation and co-localizes with K-RTA."

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"Next, confocal microscopy analysis indicated that OTUD4 distributed in both cytoplasm and nucleus in KSHV latently infected cells, while a large portion of OTUD4 translocated into the nucleus during KSHV lytic reactivation ( xref )."

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OTUD4 affects rep

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OTUD4 affects cell death

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OTUD4 activates cell death.

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"In our study, we verified that OTUD4 silence increased airway epithelial cell apoptosis and restoration of OTUD4 attenuated the CSE induced epithelia apoptosis.Although OTUD4 modulating cell death, the molecular mechanism of OTUD4 regulated cell apoptosis is still ambiguous."

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"We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death."

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"Additionally, p2 failed to disrupt the interaction between USP7-TRAF and OTUD4 (S2A Fig)."

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OTUD4 affects TRIM21

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TRIM21 binds OTUD4. 3 / 3

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"After the affinity purification by UBL7, mass spectrum results showed that UBL7 interacted with TRIM21 and OTUD4 ( Figure 5 A)."

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"Moreover, an interaction between exogenous myc-UBL7 and flag-TRIM21 or flag-OTUD4 was observed by coIP ( Figure 5 B)."

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OTUD4 affects TRAF6

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"Last, further studies are necessary to illustrate the mechanism by which OTUD4 interacts with TRAF6."

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"To investigate the relationship between OTUD4 and TRAF6, we first verified that OTUD4 interacts with TRAF6 by using coimmunoprecipitation ( Fig. 2 A)."

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OTUD4 affects TRAF1

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OTUD4 affects SMN2

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OTUD4 affects Mice

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"We found that the depletion of OTUD4 in MDA-MB-231 cells markedly suppresses lung colonization in these mice, as determined by intensity of bioluminescence ( Fig. 5 H and I) and number of lung nodules[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"OTUD4 contributes to the GBM progression in mice."

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"The expression of NOD-like receptor pyrin domain containing 3 (NLRP3) and toll- like-receptor-4 (TLR4) was assayed by IHC in the lungs and intestine in HIN1 virus-induced mice to evaluate the whole efficacy of the protective effects on lungs and intestines."

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OTUD4 affects IGF2BP3

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"These RNA-IPs showed a clear enrichment of RNA with FLAG–OTUD4 compared to that seen in control IPs ( xref C)."

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FXR2 affects OTUD4

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EIF4ENIF1 affects OTUD4

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"Co-immunoprecipitation analysis further confirmed the interaction of Otud4 with 4E-T ( Figure 5 E)."

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EGFP affects OTUD4

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"Primary rat hippocampal neurons were transfected with EGFP–OTUD4 and imaged by confocal microscopy."

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"We stained EGFP–OTUD4-expressing neurons with an anti-FMRP antibody to look for colocalization of EGFP–OTUD4 and FMRP ( xref A)."

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"EGFP–OTUD4 resided not only in the cell body but also showed prominent granular structures in proximal and distal parts of axons and in dendrites ( xref A)."

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BCA2 affects OTUD4

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BCA2 binds OTUD4.

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"In agreement with this result, overexpression of BCA2 resulted in a decreased interaction between BCA2 and OTUD4 (Fig. xref C)."

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"In agreement with this result, overexpression of BCA2 resulted in a decreased interaction between BCA2 and OTUD4 (Fig. 5C)."

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BCA2 inhibits OTUD4.

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"In addition, BCA2 prevents OTUD4, a deubiquitinating enzyme, from binding to MyD88 and removing K63 polyubiquitin chains, thereby promoting the NF-κB signaling pathway."

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ALDOA affects OTUD4

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"We further investigated whether Mir100hg regulates the interaction between ALDOA and OTUD4."

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"We further investigated whether Mir100hg regulates the interaction between ALDOA and OTUD4."

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AGO2 affects OTUD4

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"Finally, we evaluated the dimerization/oligomerization activities of OTUD4 and OTUD4 (1-425aa) and found that both OTUD4 and OTUD4 (1-425aa) could form dimer/oligomer (S6G Fig)."

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OTUD4 binds IGF2BP3 and TIAL1. 1 / 1

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"In contrast, the interaction of IGF2BP3 and TIAR with OTUD4 was even enhanced after RNase treatment ( xref E,G)."

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OTUD4 affects TDRD3

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OTUD4 affects SPINT1

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"Compared with that in the IR and IR + NC groups of mice, the inflammatory cell infiltration was ameliorated in mice overexpressing OTUD4 ( Fig. 4 C and D)."

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MYC affects OTUD4

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