IndraLab

Statements

OTUD7B affects OTUD7A
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OTUD7B binds OTUD7A. 7 / 9
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"Interestingly, a recent study showed that OTUD7A and OTUD7B interact with and modify Lys11/Lys63 heterotypic chains in order to regulate DNA damage [ xref ]."
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"In addition, Cezanne2 interacts with Cezanne ( xref D), and the DUB activity of Cezanne2 is important for its function ( xref B)."
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"Thus, Cezanne and Cezanne2 likely form a complex, with both of the DUB activities required for promoting recruitment of DNA repair factors."
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"Increased Lys11-linkage ubiquitination due to lack of Cezanne DUB activity compromises the recruitment of Rap80/BRCA1-A. Cezanne2 interacts with Cezanne, facilitating Cezanne in the recruitment of Rap80/BRCA1-A, Rad18, and 53BP1, in cellular resistance to ionizing radiation and DNA repair."
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"Cezanne2 interacts with Cezanne, playing a facilitating role in Rap80/Abraxas/BRCA1, Rad18, and 53BP1 recruitment, DNA repair, and cellular resistance to IR."
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"Thus, it is likely that Cezanne and Cezanne2 form a complex and that the DUB activity of both of these two proteins is required for promoting Rap80/Abraxas/BRCA1, Rad18, and 53BP1 recruitment.Due to the role of Cezanne and Cezanne2 in the recruitment of the Rap80/BRCA1-A complex, Rad18, and 53BP1, we examined their roles in DNA damage repair and cellular resistance to IR."
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"Cezanne2 interacts with Cezanne, promoting recruitment of Rap80/Abraxas and 53BP1 and DNA repair."
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OTUD7A affects TRAF6
1 | 3 1
OTUD7A binds TRAF6.
1 | 1 1
TRAF6 binds OTUD7A. 2 / 4
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [ xref ]."
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [XREF_BIBR]."
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OTUD7A ubiquitinates TRAF6.
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OTUD7A leads to the ubiquitination of TRAF6. 1 / 1
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"Depletion of Cezanne2 down-regulates the expression of Snail1 to impair TRAF6 deubiquitination ( Lambies et al., 2019 )."
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OTUD7A deubiquitinates TRAF6.
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OTUD7A leads to the deubiquitination of TRAF6. 1 / 1
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"Depletion of Cezanne2 down-regulates the expression of Snail1 to impair TRAF6 deubiquitination ( Lambies et al., 2019 )."
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OTUD7A affects ANK3
1 | 5
OTUD7A binds ANK3. 5 / 6
1 | 5
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"The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant."
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"OTUD7A binds to Ankyrin-G and Ankyrin-B, and shares a common PPI network."
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"These data suggest that there is a strong interaction between OTUD7A and Ankyrin-G/Ankyrin-B, and that OTUD7A may play a functional role at the ANKRD and/or spectrin-binding domain of Ankyrin-G."
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"In light of OTUD7A’s putative DUB function and our findings that the catalytic domain of OTUD7A binds to Ankyrin-G, we examined the ubiquitination status of Ankyrin-G in 15q13.3 microdeletion and OTUD7A iNeurons."
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"Given our data supporting the importance of the OTUD7A/Ankyrin-G interaction in 15q13.3 microdeletion neuronal phenotypes, as well as the observed changes in Ankyrin-G levels and stability in 15q13.3 microdeletion models, we examined whether re-expression of OTUD7A in Df(h15q13)/+ cortical neurons is sufficient to increase Ankyrin-G levels and rescue the protein homeostasis defects."
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OTUD7A affects ANK2
1 | 4 1
OTUD7A binds ANK2. 5 / 6
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"In addition, the interaction between Ankyrin-B and OTUD7A was reduced by both patient mutations, suggesting that it may also contribute to 15q13.3 microdeletion neuronal phenotypes (Fig. 3a)."
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"The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant."
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"OTUD7A binds to Ankyrin-G and Ankyrin-B, and shares a common PPI network."
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"In addition, the interaction between Ankyrin-B and OTUD7A was reduced by both patient mutations, suggesting that it may also contribute to 15q13.3 microdeletion neuronal phenotypes (Fig.  xref )."
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"These data suggest that there is a strong interaction between OTUD7A and Ankyrin-G/Ankyrin-B, and that OTUD7A may play a functional role at the ANKRD and/or spectrin-binding domain of Ankyrin-G."
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ANK3 affects OTUD7A
1 | 5
OTUD7A binds ANK3. 5 / 6
1 | 5
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"The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant."
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"OTUD7A binds to Ankyrin-G and Ankyrin-B, and shares a common PPI network."
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"These data suggest that there is a strong interaction between OTUD7A and Ankyrin-G/Ankyrin-B, and that OTUD7A may play a functional role at the ANKRD and/or spectrin-binding domain of Ankyrin-G."
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"In light of OTUD7A’s putative DUB function and our findings that the catalytic domain of OTUD7A binds to Ankyrin-G, we examined the ubiquitination status of Ankyrin-G in 15q13.3 microdeletion and OTUD7A iNeurons."
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"Given our data supporting the importance of the OTUD7A/Ankyrin-G interaction in 15q13.3 microdeletion neuronal phenotypes, as well as the observed changes in Ankyrin-G levels and stability in 15q13.3 microdeletion models, we examined whether re-expression of OTUD7A in Df(h15q13)/+ cortical neurons is sufficient to increase Ankyrin-G levels and rescue the protein homeostasis defects."
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ANK2 affects OTUD7A
1 | 4 1
OTUD7A binds ANK2. 5 / 6
1 | 4 1
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"In addition, the interaction between Ankyrin-B and OTUD7A was reduced by both patient mutations, suggesting that it may also contribute to 15q13.3 microdeletion neuronal phenotypes (Fig. 3a)."
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"The interactions between OTUD7A and Ankyrin-G (Ank3) and Ankyrin-B (Ank2) were disrupted by an epilepsy-associated OTUD7A L233F variant."
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"OTUD7A binds to Ankyrin-G and Ankyrin-B, and shares a common PPI network."
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"In addition, the interaction between Ankyrin-B and OTUD7A was reduced by both patient mutations, suggesting that it may also contribute to 15q13.3 microdeletion neuronal phenotypes (Fig.  xref )."
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"These data suggest that there is a strong interaction between OTUD7A and Ankyrin-G/Ankyrin-B, and that OTUD7A may play a functional role at the ANKRD and/or spectrin-binding domain of Ankyrin-G."
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OTUD7A affects Sarcoma, Ewing
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OTUD7A activates Sarcoma, Ewing.
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"Using artificial‐intelligence (AI)‐aided virtual drug screening, we identify the first OTUD7A catalytic inhibitor, which limits Ewing sarcoma growth in vitro and in mice by degrading EWS–FLI1.The FLI1 domain in EWS–FLI1 is targeted by SPOP and OTUD7A."
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"These data support that changes in EWS–FLI1 following OTUD7A depletion affect a subset of EWS–FLI1 transcriptional targets.2.7 Quantitative Proteomics Identifies OTUD7A Downstream Targets Mediating Ewing Sarcoma Cell Migration."
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"These data support OTUD7A as a possible EWS–FLI1 deubiquitinating enzyme to control EWS–FLI1 protein stability.2.4 Genetic Depletion of OTUD7A Impedes Ewing Sarcoma Growth."
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OTUD7A inhibits Sarcoma, Ewing.
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"Depletion of OTUD7A in Ewing sarcoma cell lines reduces EWS-FLI1 protein abundance and impedes Ewing sarcoma growth in vitro and in mice."
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"In further support of the inactivation of OTUD7A impeding Ewing sarcoma proliferation, depletion of OTUD7A resulted in significantly reduced colony formation in vitro in A673 but not A673 cells (Figure 3J,K)."
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OTUD7A affects ANK1
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OTUD7A binds ANK1. 5 / 5
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"To validate our pipeline, we followed up on a top BioID2 hit, Ankyrin-G ( Ank3 ), and found that OTUD7A interacts with Ankyrin-G and regulates its protein homeostasis."
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"These results indicate a central role for a conserved OTUD7A-Ankyrin-G interaction in neuronal dysfunction in the 15q13.3 microdeletion, providing molecular insight into disease processes."
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"We tested whether OTUD7A interacts with Ankyrin-G-190 and/or Ankyrin-B through co-immunoprecipitation of tagged proteins in HEK293 cells."
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"We next identified the protein regions of Ankyrin-G that interact with OTUD7A through co-immunoprecipitation of overexpressed HA-tagged Ankyrin-G domains and OTUD7A-FLAG in HEK293 cells."
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"While the phenotypes are not expected to be identical between mouse and human iNeuron models, both models do show a level of convergence of molecular and cellular phenotypes, supporting the notion that disruption of the OTUD7A-Ankyrin-G interaction is a key pathogenic mechanism in the 15q13.3 microdeletion."
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TRAF6 affects OTUD7A
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TRAF6 binds OTUD7A. 2 / 4
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [ xref ]."
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [XREF_BIBR]."
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"In further support of the inactivation of OTUD7A impeding Ewing sarcoma proliferation, depletion of OTUD7A resulted in significantly reduced colony formation in vitro in A673 but not A673 cells (Figure 3J,K)."
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"Like genetic OTUD7A depletion, pharmacological inhibition of OTUD7A by the compound 7Ai also decreased proliferation of Jurkat cells (Figure S20F, Supporting Information)."
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"Importantly, for all Ewing sarcoma cell lines tested, OTUD7A depletion reduced cell proliferation in vitro (Figure 3D–F)."
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OTUD7A affects SNAI1
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OTUD7A binds SNAI1.
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OTUD7A binds SNAI1. 3 / 3
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"However, MPND and Cezanne2 slightly interact with Snail1 after proteasome inhibition ( xref ) suggesting that accumulation of poly-ubiquitinated Snail1 might favor the association with these particular DUBs."
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"Here, we report that Cezanne2 expression is downregulated in HCC cells and in HCC patients' tumorous tissues and that Cezanne2 is inversely associated with Snail1 expression in HCC patients' tumorous tissues."
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"Chromatin immunoprecipitation assays and the reporter gene assay showed that Snail1 binds to the promoter of the Cezanne2 gene and mediates the direct consequence of Cezanne2 repression."
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OTUD7A increases the amount of SNAI1.
| 1
OTUD7A increases the amount of SNAI1. 1 / 1
| 1
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"Depletion of Cezanne2 down-regulates the expression of Snail1 to impair TRAF6 deubiquitination ( Lambies et al., 2019 )."
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OTUD7A affects FLI1
| 4
OTUD7A activates FLI1.
| 2
OTUD7A activates FLI1. 2 / 2
| 2
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"Remarkably, induced depletion of OTUD7A led to reduced EWS–FLI1 protein levels in multiple Ewing sarcoma cells, including A673 (Figure 3D), MHH‐ES‐1 (Figure 3E), and EWS894 (Figure 3F)."
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"These data suggest that OTUD7A/EWS–FLI1 signaling modulates a subset of EWS–FLI1 targets.In addition to characterized EWS–FLI1 target proteins whose protein abundance was controlled by OTUD7A (Figure 4D), there were additional 572 proteins downregulated by OTUD7A genetic depletion (Table S3, Supporting Information), suggesting they are potential targets for OTUD7A or uncharacterized EWS–FLI1 targets."
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OTUD7A deubiquitinates FLI1.
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OTUD7A deubiquitinates FLI1. 1 / 1
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"Consistently, both OTUD3 and OTUD7A could deubiquitinate EWS–FLI1 in cells (Figure 3C and Figure S8D,E (Supporting Information))."
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OTUD7A decreases the amount of FLI1.
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OTUD7A decreases the amount of FLI1. 1 / 1
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"MG132 treatment largely preserved EWS–FLI1 protein levels following OTUD7A depletion (Figure S9C–E, Supporting Information), further supporting a role of OTUD7A in regulating EWS–FLI1 protein stability."
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SNAI1 affects OTUD7A
| 3
OTUD7A binds SNAI1. 3 / 3
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"However, MPND and Cezanne2 slightly interact with Snail1 after proteasome inhibition ( xref ) suggesting that accumulation of poly-ubiquitinated Snail1 might favor the association with these particular DUBs."
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"Here, we report that Cezanne2 expression is downregulated in HCC cells and in HCC patients' tumorous tissues and that Cezanne2 is inversely associated with Snail1 expression in HCC patients' tumorous tissues."
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"Chromatin immunoprecipitation assays and the reporter gene assay showed that Snail1 binds to the promoter of the Cezanne2 gene and mediates the direct consequence of Cezanne2 repression."
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OTUD7A affects Mice
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OTUD7A activates Mice.
| 2
OTUD7A activates Mice. 2 / 2
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"Using artificial‐intelligence (AI)‐aided virtual drug screening, we identify the first OTUD7A catalytic inhibitor, which limits Ewing sarcoma growth in vitro and in mice by degrading EWS–FLI1.The FLI1 domain in EWS–FLI1 is targeted by SPOP and OTUD7A."
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"Uddin and colleagues combined whole-genome sequencing, human brain gene expression analysis, and study of a mouse model with a syntenic heterozygous deletion of 15q13; they found reduced expression of OTUD7A in the dendritic spine of the cortical neurons that contributed to the dendrite outgrowth abnormalities in the heterozygous 15q13 deletion mice."
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OTUD7A inhibits Mice.
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OTUD7A inhibits Mice. 1 / 1
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"Depletion of OTUD7A in Ewing sarcoma cell lines reduces EWS-FLI1 protein abundance and impedes Ewing sarcoma growth in vitro and in mice."
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OTUD7A affects EWSR1
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OTUD7A deubiquitinates EWSR1.
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OTUD7A leads to the deubiquitination of EWSR1. 1 / 1
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"In addition, 7Ai efficiently blocked OTUD7A‐mediated deubiquitination of EWS–FLI1 in cells (Figure 5C and Figure S16E (Supporting Information))."
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OTUD7A binds EWSR1.
| 1
OTUD7A binds EWSR1. 1 / 1
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"7Ai did not interfere with OTUD7A binding to EWS–FLI1 (Figure S16G, Supporting Information), suggesting this compound might suppress OTUD7A catalytic activity through interaction with the catalytic domain."
34060252
OTUD7A activates EWSR1.
| 1
OTUD7A activates EWSR1. 1 / 1
| 1
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"These data suggest that OTUD7A/EWS–FLI1 signaling modulates a subset of EWS–FLI1 targets.In addition to characterized EWS–FLI1 target proteins whose protein abundance was controlled by OTUD7A (Figure 4D), there were additional 572 proteins downregulated by OTUD7A genetic depletion (Table S3, Supporting Information), suggesting they are potential targets for OTUD7A or uncharacterized EWS–FLI1 targets."
34060252
DiUb affects OTUD7A
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DiUb binds OTUD7A. 2 / 2
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"Reactive diUb-Cez2 complex configurations were identified, which lead to isopeptide bond cleavage and stabilization of the tetrahedral oxyanion intermediate."
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"In combination with a high per-residue model confidence score (pLDDT score of 88.59 ± 14.18), the top-ranked model for the OTU domain was considered as a starting structure for Cezanne-2 and selected for subsequent refinement steps.As a model for the diUb-bound Cez2 enzyme–substrate complex, we used a combination of the AF2 prediction and structural alignment."
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Ubiquitin affects OTUD7A
| 2
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"The distal Ub–Cez2 complex structure resembled the cocrystallized Cez OTU in complex with diUb (5LRV; Figure 1)."
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"The persistent interaction between E173 of Cez2 and K33 of the substrate suggests that this is an important factor to stabilize the proximal Ub–Cez2 binding.Thus, for the third catalytic site residue E173, a similar dual functional role as for Cez can be suggested: it is critical for the recognition and stabilization of proximal Ub binding to Cez2 (for Cez2 Ub : 61% of the simulation time, for Cez2 Ub : 52%) and the stabilization of the Cys/His dyad by a water-mediated interaction with H367 as E173 makes a water bridge for ≥90% of the simulation time."
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Snail1 affects OTUD7A
| 2
Snail1 inhibits OTUD7A. 2 / 2
| 2
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"Snail1 dependent transcriptional repression of Cezanne2 in hepatocellular carcinoma."
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"Chromatin immunoprecipitation assays and the reporter gene assay showed that Snail1 binds to the promoter of the Cezanne2 gene and mediates the direct consequence of Cezanne2 repression."
23792447
Polyubiquitin affects OTUD7A
| 2
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"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor associated factor (TRAF) 6 and cleaves the polyubiquitin from TRAF6 substrates."
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [XREF_BIBR]."
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OTUD7A inhibits synapse organization. 2 / 2
| 2
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"These results suggest that OTUD7A LoF impairs synapse development and neuronal function in human neurons, providing mechanistic insight into the possible role of OTUD7A in driving neuropsychiatric phenotypes associated with the 15q13.3 deletion."
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"Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons."
35931052
OTUD7A affects diUb
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DiUb binds OTUD7A. 2 / 2
| 2
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"Reactive diUb-Cez2 complex configurations were identified, which lead to isopeptide bond cleavage and stabilization of the tetrahedral oxyanion intermediate."
39782030
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"In combination with a high per-residue model confidence score (pLDDT score of 88.59 ± 14.18), the top-ranked model for the OTU domain was considered as a starting structure for Cezanne-2 and selected for subsequent refinement steps.As a model for the diUb-bound Cez2 enzyme–substrate complex, we used a combination of the AF2 prediction and structural alignment."
39782030
OTUD7A affects cell migration
| 2
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"These data support that changes in EWS–FLI1 following OTUD7A depletion affect a subset of EWS–FLI1 transcriptional targets.2.7 Quantitative Proteomics Identifies OTUD7A Downstream Targets Mediating Ewing Sarcoma Cell Migration."
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"Intriguingly, OTUD7A depletion significantly reduced cell migration in vitro, in both A673 and A673 cells (Figure 4N,O and Figure S13C,D (Supporting Information))."
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OTUD7A affects Ubiquitin
| 2
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"The distal Ub–Cez2 complex structure resembled the cocrystallized Cez OTU in complex with diUb (5LRV; Figure 1)."
39782030
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"The persistent interaction between E173 of Cez2 and K33 of the substrate suggests that this is an important factor to stabilize the proximal Ub–Cez2 binding.Thus, for the third catalytic site residue E173, a similar dual functional role as for Cez can be suggested: it is critical for the recognition and stabilization of proximal Ub binding to Cez2 (for Cez2 Ub : 61% of the simulation time, for Cez2 Ub : 52%) and the stabilization of the Cys/His dyad by a water-mediated interaction with H367 as E173 makes a water bridge for ≥90% of the simulation time."
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OTUD7A affects UIMC1
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OTUD7A activates UIMC1. 2 / 2
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"The different roles of Cezanne and Cezanne2 in promoting Rap80 or Rad18 and 53BP1 suggest that the K63-dependent recruitments of DNA repair proteins are differentially regulated by Cezanne and Cezanne2."
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"These data indicate that both Cezanne and Cezanne2 are required to recruit 53BP1 to DNA damage sites.The defects caused by the deficiency of Cezanne2 in recruiting Rap80 and 53BP1 can be rescued by expression of Cezanne2 WT but not the DUB mutant (Cez2-CS) (Fig. 7C), indicating that the DUB activity of Cezanne2 is required for its function."
31699778
OTUD7A affects TP53BP1
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OTUD7A activates TP53BP1. 2 / 2
| 2
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"The different roles of Cezanne and Cezanne2 in promoting Rap80 or Rad18 and 53BP1 suggest that the K63-dependent recruitments of DNA repair proteins are differentially regulated by Cezanne and Cezanne2."
31699778
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"These data indicate that both Cezanne and Cezanne2 are required to recruit 53BP1 to DNA damage sites.The defects caused by the deficiency of Cezanne2 in recruiting Rap80 and 53BP1 can be rescued by expression of Cezanne2 WT but not the DUB mutant (Cez2-CS) (Fig. 7C), indicating that the DUB activity of Cezanne2 is required for its function."
31699778
OTUD7A affects Polyubiquitin
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"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor associated factor (TRAF) 6 and cleaves the polyubiquitin from TRAF6 substrates."
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"They indicated that Cezanne2 interacted with TRAF6 and cleaved the polyubiquitin from TRAF6 substrates whose suppression might have a key role in the HCC malignancy transformation [XREF_BIBR]."
27708550
OTUD7A affects EWS-FLI1 protein
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OTUD7A activates EWS-FLI1 protein. 2 / 2
| 2
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"Enhancing SPOP activity and deleting OTUD7A could reduce EWS-FLI1 protein abundance and thus hinder Ewing sarcoma growth in vitro and in vivo 65."
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"Depletion of OTUD7A in Ewing sarcoma cell lines reduces EWS-FLI1 protein abundance and impedes Ewing sarcoma growth in vitro and in mice."
34060252
OTUD7A affects BioID2
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OTUD7A binds BioID2. 2 / 2
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"Following validation of the construct (Supplementary Fig.  xref ), we identified 12 Ankyrin-G-190 protein interactors in mouse cortical neurons, of which seven proteins were shared with the OTUD7A-BioID2 protein interactome (Fig.  xref ), suggesting that OTUD7A and Ankyrin-G partially share a PPI network."
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"It is important to note that the abundance of OTUD7A itself was decreased by about 30%, which could be due to decreased expression of the OTUD7A L233F-BioID2 itself and/or reduced binding of the fusion protein to endogenous mouse OTUD7A (Supplementary Table  xref )."
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OTUD7A affects Ankyrin-G-270
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OTUD7A increases the amount of Ankyrin-G-270. 1 / 1
| 1
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"Expression of OTUD7A N492_K494del or OTUD7A L233F was able to increase levels of Ankyrin-G-270 but did not increase levels of Ankyrin-G-190 (Fig. 7e–g), suggesting that patient mutations may specifically affect the ability of OTUD7A to regulate the 190 kDa isoform of Ankyrin-G-190."
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OTUD7A-L233F increases the amount of Ankyrin-G-270. 1 / 1
| 1
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"Expression of OTUD7A N492_K494del or OTUD7A L233F was able to increase levels of Ankyrin-G-270 but did not increase levels of Ankyrin-G-190 (Fig. 7e–g), suggesting that patient mutations may specifically affect the ability of OTUD7A to regulate the 190 kDa isoform of Ankyrin-G-190."
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OTUD7A affects Ankyrin-G-190
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OTUD7A-L233F increases the amount of Ankyrin-G-190. 1 / 1
| 1
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"Expression of OTUD7A N492_K494del or OTUD7A L233F was able to increase levels of Ankyrin-G-270 but did not increase levels of Ankyrin-G-190 (Fig. 7e–g), suggesting that patient mutations may specifically affect the ability of OTUD7A to regulate the 190 kDa isoform of Ankyrin-G-190."
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OTUD7A increases the amount of Ankyrin-G-190. 1 / 1
| 1
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"Expression of OTUD7A N492_K494del or OTUD7A L233F was able to increase levels of Ankyrin-G-270 but did not increase levels of Ankyrin-G-190 (Fig. 7e–g), suggesting that patient mutations may specifically affect the ability of OTUD7A to regulate the 190 kDa isoform of Ankyrin-G-190."
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OTUD7A affects 3XFLAG
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3XFLAG binds OTUD7A. 2 / 2
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"We first observed that levels of OTUD7A N492_K494del-3XFLAG were significantly higher than WT OTUD7A-3XFLAG (after normalizing for transduction efficiency), whereas levels of OTUD7A L233F-3XFLAG were not statistically different from WT OTUD7A-3XFLAG levels (Fig.  xref )."
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"Expression of WT OTUD7A-3XFLAG significantly increased levels of Ankyrin-G-270 and Ankyrin-G-190 compared to Df(h15q13)/+ neurons transduced with TurboGFP (Fig.  xref )."
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EWSR1 affects OTUD7A
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EWSR1 binds OTUD7A.
| 1
OTUD7A binds EWSR1. 1 / 1
| 1
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"7Ai did not interfere with OTUD7A binding to EWS–FLI1 (Figure S16G, Supporting Information), suggesting this compound might suppress OTUD7A catalytic activity through interaction with the catalytic domain."
34060252
EWSR1 activates OTUD7A.
| 1
EWSR1 activates OTUD7A. 1 / 1
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"To further reinforce this notion, we also expressed EWS–FLI1‐3A in both EWS894‐teton‐shOTUD7A (Figure S11L,M, Supporting Information) and MHH‐ES‐1‐teton‐shOTUD7A cells (Figure S11O,P, Supporting Information) and found that EWS–FLI1‐3A largely rescued OTUD7A‐depletion‐induced growth retardation in both cell lines (Figure S11N,Q, Supporting Information)."
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BioID2 affects OTUD7A
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OTUD7A binds BioID2. 2 / 2
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sparser
"Following validation of the construct (Supplementary Fig.  xref ), we identified 12 Ankyrin-G-190 protein interactors in mouse cortical neurons, of which seven proteins were shared with the OTUD7A-BioID2 protein interactome (Fig.  xref ), suggesting that OTUD7A and Ankyrin-G partially share a PPI network."
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sparser
"It is important to note that the abundance of OTUD7A itself was decreased by about 30%, which could be due to decreased expression of the OTUD7A L233F-BioID2 itself and/or reduced binding of the fusion protein to endogenous mouse OTUD7A (Supplementary Table  xref )."
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3XFLAG affects OTUD7A
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3XFLAG binds OTUD7A. 2 / 2
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"We first observed that levels of OTUD7A N492_K494del-3XFLAG were significantly higher than WT OTUD7A-3XFLAG (after normalizing for transduction efficiency), whereas levels of OTUD7A L233F-3XFLAG were not statistically different from WT OTUD7A-3XFLAG levels (Fig.  xref )."
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"Expression of WT OTUD7A-3XFLAG significantly increased levels of Ankyrin-G-270 and Ankyrin-G-190 compared to Df(h15q13)/+ neurons transduced with TurboGFP (Fig.  xref )."
36604605
MCherry affects OTUD7A
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sparser
"Fluorescence intensities of WT OTUD7A-mCherry and OTUD7A L233F-mCherry in neurons were the same (Supplementary Fig.  xref ), suggesting that the variant does not change OTUD7A protein levels."
36604605
UBD affects OTUD7A
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UBD binds OTUD7A. 1 / 1
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"Structural and conformational dynamics of apo Cez2 (Cez2apo) and diubiquitin-bound Cez2 (Cez2Ub ) were investigated using MD simulations for a total of 12 μs."
39782030
trips
"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor-associated factor (TRAF)6 and cleaves the polyubiquitin from TRAF6 substrates."
23792447
TNF receptor affects OTUD7A
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OTUD7A binds TNF receptor. 1 / 1
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"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor associated factor (TRAF) 6 and cleaves the polyubiquitin from TRAF6 substrates."
23792447
Sarcoma, Ewing affects OTUD7A
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"These results motivated us to search for potential small molecules that would inhibit OTUD7A catalytic activity as a possible therapeutic strategy for Ewing sarcoma.2.8 OTUD7A is Expressed across Tissues, Including Ewing Sarcoma Tumors."
34060252
Rap80/Abraxas/BRCA1 affects OTUD7A
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Rap80/Abraxas/BRCA1 bound to RAD18 inhibits OTUD7A. 1 / 1
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"Thus, Cezanne2 facilitates Cezanne in regulating Rap80/Abraxas/BRCA1 and Rad18 recruitment.Whereas knockdown of either Cezanne or Cezanne2 alone did not result in much change in 53BP1 IRIF (Fig. 7B; Supplemental Fig. S8), depletion of both genes by siRNAs, however, led to a significant decrease in 53BP1 IRIF (Fig. 7B)."
31699778
OTUD7A affects mCherry
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sparser
"Fluorescence intensities of WT OTUD7A-mCherry and OTUD7A L233F-mCherry in neurons were the same (Supplementary Fig.  xref ), suggesting that the variant does not change OTUD7A protein levels."
36604605
reach
"Given our data supporting the importance of the OTUD7A/Ankyrin-G interaction in 15q13.3 microdeletion neuronal phenotypes, as well as the observed changes in Ankyrin-G levels and stability in 15q13.3 microdeletion models, we examined whether re-expression of OTUD7A in Df(h15q13)/+ cortical neurons is sufficient to increase Ankyrin-G levels and rescue the protein homeostasis defects."
36604605
reach
"Sholl analysis revealed that re-expression of OTUD7A in 15q13.3 microdeletion iNeurons increased dendrite arborization back to familial control levels, indicating that re-expression of OTUD7A is sufficient to rescue morphological defects in human 15q13.3 microdeletion glutamatergic neurons (Fig. 7b, c)."
36604605
OTUD7A affects cell growth
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OTUD7A activates cell growth. 1 / 1
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"As predicted, reconstitution of FLI1‐3A expression in A673‐teton‐shOTUD7A cells (Figure S11G,H, Supporting Information) could not rescue OTUD7A‐depletion‐induced A673 cell growth retardation in vitro (Figure S11I–K, Supporting Information)."
34060252
OTUD7A affects cell death
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OTUD7A inhibits cell death. 1 / 1
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"Stable OTUD7A depletion led to cell death within a week of shRNA or sgRNA infection, preventing us from further analyzing the signaling changes and biological effects of OTUD7A loss."
34060252
OTUD7A affects UBD
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UBD binds OTUD7A. 1 / 1
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reach
"Structural and conformational dynamics of apo Cez2 (Cez2apo) and diubiquitin-bound Cez2 (Cez2Ub ) were investigated using MD simulations for a total of 12 μs."
39782030
OTUD7A affects TP53
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OTUD7A decreases the amount of TP53. 1 / 1
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"Interestingly, the transfection of BAP1 siRNA, and not OTUD7A and OTUB1 siRNAs, still upregulated p53 expression in ODN-treated Caki-1 cells (Fig. 6A)."
35584569
trips
"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor-associated factor (TRAF)6 and cleaves the polyubiquitin from TRAF6 substrates."
23792447
OTUD7A affects TNF receptor
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OTUD7A binds TNF receptor. 1 / 1
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reach
"Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor associated factor (TRAF) 6 and cleaves the polyubiquitin from TRAF6 substrates."
23792447
OTUD7A affects Syndrome
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OTUD7A inhibits Syndrome. 1 / 1
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"Possibly, a heterozygous deletion of OTUD7A leads to a disruption of the ubiquitination pathway and contributes to the phenotypic overlap between patients with AS and patients with the 15q13.3 deletio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20382277
OTUD7A affects SPOP
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OTUD7A inhibits SPOP. 1 / 1
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"The deubiquitinase OTUD7A antagonizes SPOP function to stabilize EWS–FLI1, revealing OTUD7A as a new Ewing‐sarcoma‐growth‐dependent gene."
34060252
OTUD7A affects SP1
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OTUD7A decreases the amount of SP1. 1 / 1
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"OTUB1, OTUD7A, and BAP1 downregulated Sp1 and Bax expression (Fig. 5)."
35584569
OTUD7A affects SOX2
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OTUD7A ubiquitinates SOX2. 1 / 1
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"ShRNA targeting OTUD7B but not OTUD7A increased Sox2 ubiquitylation (Fig.  xref )."
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OTUD7A affects RAD18
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OTUD7A activates RAD18. 1 / 1
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"The different roles of Cezanne and Cezanne2 in promoting Rap80 or Rad18 and 53BP1 suggest that the K63-dependent recruitments of DNA repair proteins are differentially regulated by Cezanne and Cezanne2."
31699778
OTUD7A affects Otud7a mice
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OTUD7A activates Otud7a mice. 1 / 1
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reach
"The 15q13.2-q13.3 deletion credible interval includes the haploinsufficient gene OTUD7A, shown to cause abnormal development of cortical dendritic spines and dendrite outgrowth in Otud7a mice , and KLF13, shown to cause a layer-specific decrease of cortical interneurons in Klf13 mice ."
37474567
OTUD7A affects OTUD6B
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OTUD6B binds OTUD7A. 1 / 1
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"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD7A affects OTUD4
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OTUD4 binds OTUD7A. 1 / 1
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"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD7A affects OTUD3
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OTUD3 binds OTUD7A. 1 / 1
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"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD7A affects OTUB1
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OTUD7A inhibits OTUB1. 1 / 1
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"OTUD7A expression was significantly decreased in AS, GBM, and ODG (Figure 4), as was OTUB1 in all three types of gliomas compared to non-tumor tissues in the Sun dataset (Table 1)."
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OTUD7A activates Nervous System Diseases. 1 / 1
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"52 Although it remains unclear if these neurological disorders caused by OTUD7A dysfunction are limited to changes in dendritic spines, these results offer additional considerations if 7Ai or other OTUD7A inhibitors begin preclinical evaluation for Ewing sarcoma.Our studies demonstrated efficacy of 7Ai in vivo and in vitro efficacy in the micromolar range."
34060252
OTUD7A affects Neoplasms
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OTUD7A activates Neoplasms. 1 / 1
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reach
"Moreover, depletion of OTUD7A dramatically reduced tumor growth (Figure 3L) and tumor formation of A673 (Figure 3M,N), but not A673 (Figure S10A–C, Supporting Information) cells grown as xenografts."
34060252
OTUD7A affects Muscle Hypotonia
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OTUD7A inhibits Muscle Hypotonia. 1 / 1
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"For instance, a biallelic loss of OTUD7A causes severe muscular hypotonia associated with intellectual disability and seizures in humans [23] (Table 1)."
38716888
OTUD7A affects KLF13
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OTUD7A activates KLF13. 1 / 1
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"The 15q13.2-q13.3 deletion credible interval includes the haploinsufficient gene OTUD7A, shown to cause abnormal development of cortical dendritic spines and dendrite outgrowth in Otud7a mice , and KLF13, shown to cause a layer-specific decrease of cortical interneurons in Klf13 mice ."
37474567
OTUD7A affects K63-di-Ub
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OTUD7A binds K63-di-Ub. 1 / 1
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"Analyzing the UBA domain from Cezanne or Cezanne2 binding to K63-di-Ub in vitro using isothermal titration calorimetry (ITC) showed that both of the UBA domains bind to K63-di-Ub, with a binding affinity (K = 20 ± 2 and 20 ± 5 μM), approximately threefold lower than that of the UIMs of Rap80 (K = 6.4 ± 0.2 μM) (Fig. 1C)."
31699778
OTUD7A affects Glu-Ser
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OTUD7A activates Glu-Ser. 1 / 1
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"Remarkably, induced depletion of OTUD7A led to reduced EWS–FLI1 protein levels in multiple Ewing sarcoma cells, including A673 (Figure 3D), MHH‐ES‐1 (Figure 3E), and EWS894 (Figure 3F)."
34060252
OTUD7A affects Glioma
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OTUD7A inhibits Glioma. 1 / 1
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"OTUD7A expression was significantly decreased in AS, GBM, and ODG (Figure 4), as was OTUB1 in all three types of gliomas compared to non-tumor tissues in the Sun dataset (Table 1)."
37892185
OTUD7A affects FlaG
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FlaG binds OTUD7A. 1 / 1
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"We next identified the protein regions of Ankyrin-G that interact with OTUD7A through co-immunoprecipitation of overexpressed HA-tagged Ankyrin-G domains and OTUD7A-FLAG in HEK293 cells."
36604605
OTUD7A affects EWS894
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OTUD7A inhibits EWS894. 1 / 1
| 1
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"Remarkably, induced depletion of OTUD7A led to reduced EWS–FLI1 protein levels in multiple Ewing sarcoma cells, including A673 (Figure 3D), MHH‐ES‐1 (Figure 3E), and EWS894 (Figure 3F)."
34060252
OTUD7A affects EWS-FLI1
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OTUD7A deubiquitinates EWS-FLI1. 1 / 1
| 1
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"Opposing this process, OTUD7A deubiquitinates and stabilizes EWS-FLI1."
34060252
OTUD7A affects EWS-FLI1 Transcriptional Targets
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OTUD7A decreases the amount of EWS-FLI1 Transcriptional Targets. 1 / 1
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"Consistent with EWS–FLI1 signaling being a major OTUD7A downstream effector, more than one tenth (62) of the downregulated proteins exert DNA‐binding transcriptional activity (Figure S12D, Supporting Information), many of which have been characterized to associate with EWS–FLI1 on chromatin, including CBP, forkhead box proteins, and zinc finger proteins.2.6 Genetic OTUD7A Inactivation Reduces Expression of EWS-FLI1 Transcriptional Targets."
34060252
OTUD7A affects ETS2
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OTUD7A activates ETS2. 1 / 1
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"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."
37892157
OTUD7A affects EGFR
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OTUD7A activates EGFR. 1 / 1
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"Accordingly, simultaneous knockdown of Cezanne-1 and Cezanne-2 by using two pools of four oligonucleotides (approximately 70% and 50%, respectively) moderately enhanced both basal and inducible degradation of EGFR, whereas the reciprocal silencing of c-CBL and CBL-b showed the expected opposite effect (XREF_FIG)."
22179831
reach
"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."
37892157
OTUD7A affects Circulin-C
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OTUD7A binds Circulin-C. 1 / 1
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sparser
"Circ-OTUD7A is highly expressed in DLBCL, and knockdown of circ-OTUD7A inhibits DLBCL cell proliferation and metastasis, promoting cell cycle arrest and apoptosis."
35116058
OTUD7A affects CHRNA7
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OTUD7A activates CHRNA7. 1 / 1
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"We previously demonstrated that re-expression of OTUD7A in vivo rescues dendritic growth defects in mouse cortical neurons [30], whereas another study stimulated CHRNA7 using an alpha7 positive allosteric modulator [100]."
36604605
OTUD7A affects CFD
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OTUD7A activates CFD. 1 / 1
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"Sholl analysis revealed that WT OTUD7A rescued dendrite complexity in Df(h15q13)/+ neurons, whereas OTUD7A L233F did not, indicating that the OTUD7A L233F variant affects the ability of OTUD7A to regulate dendrite complexity (Fig. 2e–g)."
36604605
OTUD7A affects BAX
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OTUD7A decreases the amount of BAX. 1 / 1
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"OTUB1, OTUD7A, and BAP1 downregulated Sp1 and Bax expression (Fig. 5)."
35584569
OTUD7A affects 3A
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OTUD7A increases the amount of 3A. 1 / 1
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"As a result, unlike WT‐EWS–FLI1, OTUD7A depletion failed to significantly impede 3A‐EWS–FLI1 expressing A673 cell growth in vitro (Figure S11C,D, Supporting Information) and as a xenograft (Figure S11E,F, Supporting Information)."
34060252
OTUD6B affects OTUD7A
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OTUD6B binds OTUD7A. 1 / 1
| 1
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"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD4 affects OTUD7A
| 1
OTUD4 binds OTUD7A. 1 / 1
| 1
reach
"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
OTUD3 affects OTUD7A
| 1
OTUD3 binds OTUD7A. 1 / 1
| 1
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"We found that OTUD3, OTUD4, OTUD6B, and OTUD7A bound to EWS–FLI1 in cells (Figure 3B)."
34060252
Neoplasms affects OTUD7A
| 1
Neoplasms inhibits OTUD7A. 1 / 1
| 1
reach
"These results motivated us to search for potential small molecules that would inhibit OTUD7A catalytic activity as a possible therapeutic strategy for Ewing sarcoma.2.8 OTUD7A is Expressed across Tissues, Including Ewing Sarcoma Tumors."
34060252
K63-di-Ub affects OTUD7A
| 1
OTUD7A binds K63-di-Ub. 1 / 1
| 1
reach
"Analyzing the UBA domain from Cezanne or Cezanne2 binding to K63-di-Ub in vitro using isothermal titration calorimetry (ITC) showed that both of the UBA domains bind to K63-di-Ub, with a binding affinity (K = 20 ± 2 and 20 ± 5 μM), approximately threefold lower than that of the UIMs of Rap80 (K = 6.4 ± 0.2 μM) (Fig. 1C)."
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FlaG affects OTUD7A
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FlaG binds OTUD7A. 1 / 1
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sparser
"We next identified the protein regions of Ankyrin-G that interact with OTUD7A through co-immunoprecipitation of overexpressed HA-tagged Ankyrin-G domains and OTUD7A-FLAG in HEK293 cells."
36604605
FLI1 affects OTUD7A
| 1
FLI1 inhibits OTUD7A. 1 / 1
| 1
reach
"These data support OTUD7A as a possible EWS–FLI1 deubiquitinating enzyme to control EWS–FLI1 protein stability.2.4 Genetic Depletion of OTUD7A Impedes Ewing Sarcoma Growth."
34060252
Circulin-C affects OTUD7A
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OTUD7A binds Circulin-C. 1 / 1
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sparser
"Circ-OTUD7A is highly expressed in DLBCL, and knockdown of circ-OTUD7A inhibits DLBCL cell proliferation and metastasis, promoting cell cycle arrest and apoptosis."
35116058
ARHGAP11B affects CHRNA7, FAN1, KLF13, OTUD7A, and TRPM1
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sparser
"Our data support associations of schizophrenia with 1.5-Mb deletions containing ARHGAP11B, MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, and CHRNA7."
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