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OTUD6A affects CDC6
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OTUD6A binds CDC6.
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OTUD6A binds CDC6. 10 / 12
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"We further investigated the role of interaction between CDC6 and OTUD6A in CDC6 protein regulation."
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"Although mutation of OTUD6A did not affect the interaction between OTUD6A and CDC6 (Supplementary Fig.  xref h), the C152A mutant of OTUD6A lost the ability to upregulate CDC6 (Fig.  xref h, i and Supplementary Fig.  xref i-m)."
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"OTUD6A directly interacts with CDC6."
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"Through a screening of DUBs, we found that OTUD6A interacts with CDC6 and increases the CDC6 protein level by promoting the stability of CDC6 through removing polyubiquitin chains, whose attachment was mediated by SCF-Cyclin F and APC/C-CDH1 (Fig.  xref )."
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"However, overexpression of OTUD6A-C-terminus, which could not interact with CDC6, lost its ability to promote cell proliferation (Supplementary Fig.  xref f-h)."
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"However, the interaction between CDC6 and OTUD6A was not changed in cells treated with the CDK2 inhibitor CVT-313 compared with that in control cells (Supplementary Fig.  xref j)."
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"We showed that DNA damage promotes the binding of OTUD6A to CDC6, subsequently upregulating CDC6 protein level, activating the ATR-Chk1 pathway and resulting in chemoresistance (Fig.  xref )."
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"We next examined whether OTUD6A physically interacts with CDC6."
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"Bimolecular fluorescent complimentary (BiFC) assays confirmed that OTUD6A directly interacts with CDC6 (Fig.  xref f)."
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"GST pulldown and assays confirmed the direct interaction between the N-terminal region of OTUD6A and CDC6 (Fig.  xref g)."
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OTUD6A binds CDC6. 8 / 8
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"We showed that DNA damage promotes the binding of OTUD6A to CDC6, subsequently upregulating CDC6 protein level, activating the ATR-Chk1 pathway and resulting in chemoresistance (Fig. 8)."
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"Tissue specimens were used to determine the association between OTUD6A and CDC6."
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"OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination."
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"Importantly, the interaction between OTUD6A and CDC6 was detected in late S phase and occurred predominantly in G2/M phase, following the same trend as CDC6 protein level (Fig. 2h, i)."
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"HU treatment, which increased CDC6 expression, effectively promoted the interaction between OTUD6A and CDC6, indicating that replication stress enhanced the binding capacity between OTUD6A and CDC6 (Fig. 2j)."
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"However, the interaction between CDC6 and OTUD6A was not changed in cells treated with the CDK2 inhibitor CVT-313 compared with that in control cells (Supplementary Fig. 2j)."
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"Although mutation of OTUD6A did not affect the interaction between OTUD6A and CDC6 (Supplementary Fig. 3h), the C152A mutant of OTUD6A lost the ability to upregulate CDC6 (Fig. 3h, i and Supplementary Fig. 3i-m)."
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"We further investigated the role of interaction between CDC6 and OTUD6A in CDC6 protein regulation."
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OTUD6A increases the amount of CDC6.
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OTUD6A increases the amount of CDC6. 10 / 12
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"Depletion of OTUD6A inhibits CDC6 expression as well as BBN-induced BCa tumorigenesis and tumour progression."
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"Collectively, these results demonstrate that OTUD6A positively regulates the CDC6 protein level both in vivo and in vitro."
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"Immunofluorescence (IF) staining further confirmed that overexpression of the OTUD6A upregulated the endogenous CDC6 protein level, compared to those transfected with empty Flag vector and Flag-OTUD6A untransfected cells (Fig. 1d), and transient transfection with empty Flag vector or Flag-OTUD6A plasmid didn’t change the cell cycle distribution (Supplementary Fig. 1b)."
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"Thus we fractionated cell lysates into cytoplasmic, soluble and chromatin-bound fractions, and found that overexpression of OTUD6A increased while knockdown of OTUD6A decreased the CDC6 protein level in all three fractions (Fig. 1g and Supplementary Fig. 1m, n)."
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"Through a screening of DUBs, we found that OTUD6A interacts with CDC6 and increases the CDC6 protein level by promoting the stability of CDC6 through removing polyubiquitin chains, whose attachment was mediated by SCF-Cyclin F and APC/C-CDH1 (Fig. 8)."
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"Our results confirmed that the changes in the levels of CDC6 protein caused by OTUD6A were not results from changes in the cell cycle."
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"Here, we found that OTUD6A upregulated CDC6 protein level in several types of cancer cells."
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"Notably, knockout of OTUD6A resulted in less bladder tumorigenesis, lower malignancy and a lower CDC6 protein level upon BBN treatment (Fig. 5r-t), indicating that knockout of OTUD6A inhibited BCa tumorigenesis and CDC6 expression induced by chemical carcinogen."
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"The finding that OTUD6A increases the CDC6 protein level but does not affect the CDC6 mRNA level suggests that OTUD6A regulates CDC6 expression at the posttranscriptional level."
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"Overexpression of OTUD6A upregulated CDC6 protein level and prolonged the half-life of the CDC6 protein, independent of its phosphorylation status (Supplementary Fig. 3c-e)."
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OTUD6A activates CDC6.
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OTUD6A activates CDC6. 7 / 7
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"Taken together, these data demonstrated that OTUD6A maintains CDC6 stability, removes K6-, K33- and K48-linked polyubiquitin chains, and reverses CDC6 degradation caused by APC/C-CDH1 and SCF-Cyclin F. OTUD6A participates in cell cycle progression by regulating CDC6."
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"Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6."
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"The upregulation of CDC6 by OTUD6A was not due to changes in the cell cycle as neither stable overexpression nor knockdown of OTUD6A influenced the cell cycle distribution in asynchronous cells (Supplementary Fig. 1k, l)."
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"Moreover, knockdown of OTUD6A was accompanied by decreased loading of MCM2, a subunit of pre-RC, onto chromatin (Fig. 1h), suggesting that knockdown of OTUD6A prevents pre-RC assembly.To confirm the role of OTUD6A in CDC6 regulation in vivo, we crossed Otud6a mice with Dppa3-Cre (which exert efficient Cre recombination enzyme activity during the early stage of embryonic development and in germ cell line [30]) mice to generate conditional Otud6a knockout (CKO) mice (Supplementary Fig. 1o, p)."
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"The half-life of the endogenous CDC6 protein was prolonged in OTUD6A-overexpressing cells (Fig. 3a), whereas knockdown or knockout of OTUD6A led to a shortened half-life (Fig. 3b, c and Supplementary Fig. 3a), suggesting that OTUD6A inhibits CDC6 degradation."
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"Overexpression of OTUD6A upregulated CDC6 protein level and prolonged the half-life of the CDC6 protein, independent of its phosphorylation status (Supplementary Fig. 3c-e)."
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"Ubiquitin-proteasome system and the autophagy-lysosome pathway are the two main mechanisms responsible for intracellular protein degradation [34], we next clarified the pathway involved in OTUD6A-mediated CDC6 regulation."
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OTUD6A deubiquitinates CDC6.
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OTUD6A deubiquitinates CDC6. 3 / 3
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"Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance."
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"Conversely, knockdown of OTUD6A increased the polyubiquitination of CDC6 (Fig. 3g)."
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"Indeed, overexpression of OTUD6A markedly reduced endogenous and exogenous CDC6 polyubiquitination in cells (Fig. 3e and Supplementary Fig. 3g)."
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CDC6 affects OTUD6A
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CDC6 binds OTUD6A.
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OTUD6A binds CDC6. 10 / 12
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"We further investigated the role of interaction between CDC6 and OTUD6A in CDC6 protein regulation."
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"Although mutation of OTUD6A did not affect the interaction between OTUD6A and CDC6 (Supplementary Fig.  xref h), the C152A mutant of OTUD6A lost the ability to upregulate CDC6 (Fig.  xref h, i and Supplementary Fig.  xref i-m)."
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"OTUD6A directly interacts with CDC6."
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"Through a screening of DUBs, we found that OTUD6A interacts with CDC6 and increases the CDC6 protein level by promoting the stability of CDC6 through removing polyubiquitin chains, whose attachment was mediated by SCF-Cyclin F and APC/C-CDH1 (Fig.  xref )."
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"However, overexpression of OTUD6A-C-terminus, which could not interact with CDC6, lost its ability to promote cell proliferation (Supplementary Fig.  xref f-h)."
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"However, the interaction between CDC6 and OTUD6A was not changed in cells treated with the CDK2 inhibitor CVT-313 compared with that in control cells (Supplementary Fig.  xref j)."
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"We showed that DNA damage promotes the binding of OTUD6A to CDC6, subsequently upregulating CDC6 protein level, activating the ATR-Chk1 pathway and resulting in chemoresistance (Fig.  xref )."
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"We next examined whether OTUD6A physically interacts with CDC6."
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"Bimolecular fluorescent complimentary (BiFC) assays confirmed that OTUD6A directly interacts with CDC6 (Fig.  xref f)."
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"GST pulldown and assays confirmed the direct interaction between the N-terminal region of OTUD6A and CDC6 (Fig.  xref g)."
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OTUD6A binds CDC6. 8 / 8
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"We showed that DNA damage promotes the binding of OTUD6A to CDC6, subsequently upregulating CDC6 protein level, activating the ATR-Chk1 pathway and resulting in chemoresistance (Fig. 8)."
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"Tissue specimens were used to determine the association between OTUD6A and CDC6."
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"OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination."
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"Importantly, the interaction between OTUD6A and CDC6 was detected in late S phase and occurred predominantly in G2/M phase, following the same trend as CDC6 protein level (Fig. 2h, i)."
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"HU treatment, which increased CDC6 expression, effectively promoted the interaction between OTUD6A and CDC6, indicating that replication stress enhanced the binding capacity between OTUD6A and CDC6 (Fig. 2j)."
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"However, the interaction between CDC6 and OTUD6A was not changed in cells treated with the CDK2 inhibitor CVT-313 compared with that in control cells (Supplementary Fig. 2j)."
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"Although mutation of OTUD6A did not affect the interaction between OTUD6A and CDC6 (Supplementary Fig. 3h), the C152A mutant of OTUD6A lost the ability to upregulate CDC6 (Fig. 3h, i and Supplementary Fig. 3i-m)."
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"We further investigated the role of interaction between CDC6 and OTUD6A in CDC6 protein regulation."
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CDC6 decreases the amount of OTUD6A.
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CDC6 decreases the amount of OTUD6A. 1 / 1
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"Similar to that of OTUD6A overexpression, CDC6 overexpression decreased the chemosensitivity and promoted gemcitabine-induced ATR and Chk1 activation in UMUC3 cells (Supplementary Fig. 11g-k)."
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CDC6 activates OTUD6A.
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CDC6 activates OTUD6A. 1 / 1
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"Moreover, ectopic expression of CDC6 effectively reversed the OTUD6A knockdown-mediated tumour growth inhibition in vivo (Fig. 5o, p and Supplementary Fig. 8m, n)."
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OTUD6A affects Aurora-A
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OTUD6A activates Aurora-A.
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OTUD6A activates Aurora-A. 5 / 5
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"Notably , OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A ."
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"Therefore , OTUD6A was selected as a DUB that binds to , deubiquitinates , and activates Aurora-A ."
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"Consequently , our data suggest that Aurora-A , a critical mitotic regulator , is deubiquitinated , stabilized , and activated by OTUD6A , which in turn activates PLK1 to drive cells into mitosis ."
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"Notably, OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A."
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"OTUD6A Promotes Protein Stability and Kinase Activity of Aurora-A."
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OTUD6A deubiquitinates Aurora-A.
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OTUD6A deubiquitinates Aurora-A. 4 / 4
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"OTUD6A Deubiquitinates Aurora-A."
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"Only OTUD1 and OTUD6A induced the deubiquitination of Aurora-A (XREF_FIG a)."
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"OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A."
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"We found that OTUD6A deubiquitinates Aurora-A to stabilize and activate by interacting through the kinase domain of Aurora-A."
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OTUD6A binds Aurora-A.
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OTUD6A binds Aurora-A. 3 / 3
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"To confirm the interaction between Aurora-A and OTUD6A, we conducted reverse co-immunoprecipitation by pulling down MYC tagged Aurora-A from the transfected HEK293T cell lysate and subsequently immunoblotted SFB tagged OTUD6A with FLAG antibody."
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"As shown in XREF_FIG b, OTUD6A indeed interacted with Aurora-A."
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"OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A."
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OTUD6A affects DNM1L
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OTUD6A deubiquitinates DNM1L.
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OTUD6A deubiquitinates DNM1L. 3 / 4
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"For instance, OTUD6A deubiquitinates and stabilizes Drp1 to regulate mitochondrial morphology in colon cancer, and it plays a critical role in promoting tumor cell resistance to chemoradiotherapy by deubiquitinating and stabilizing TopBP1 [35,36]."
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"OTUD6A interacts with and deubiquitinates Drp1 to enhance mitochondrial fission [49]."
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"Furthermore, overexpression of deubiquitinating enzyme 6A (OTUD6A) promotes deubiquitination of Drp1, which increases proliferation and cloning of CRC cells."
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OTUD6A binds DNM1L.
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DNM1L binds OTUD6A. 1 / 3
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"OTUD6A interacts with and deubiquitinates Drp1 to enhance mitochondrial fission [49]."
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OTUD6A increases the amount of DNM1L.
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Modified OTUD6A increases the amount of DNM1L. 1 / 1
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"Conversely, overexpression of OTUD6A increases Drp1 levels and its protein half-life and enhances cancer cell growth."
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OTUD6A decreases the amount of DNM1L.
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OTUD6A decreases the amount of DNM1L. 1 / 1
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"Depletion of OTUD6A leads to lower Drp1 levels and suppressed mitochondrial fission and the affected cells are consequently less prone to tumorigenesis."
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OTUD6A activates DNM1L.
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OTUD6A activates DNM1L. 1 / 1
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"Deubiquitinating enzyme ovarian tumor-associated protease deubiquitinase 6A (OTUD6A) cleaves off ubiquitin residues and increases DRP1 stability in the cell."
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OTUD6A activates cell population proliferation. 5 / 8
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"Knockdown of OTUD6A inhibited the cell proliferation (Fig. 4d, e)."
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"Moreover, OTUD6A is expressed at high levels in breast cancer, and OTUD6A overexpression promotes cell proliferation, migration and invasion, indicating that dysregulation of OTUD6A expression contributes to genomic instability and is associated with tumor development."
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"Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6."
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"Deubiquitinase OTUD6A promotes proliferation of cancer cells via regulating Drp1 stability and mitochondrial fission."
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"We further showed that OTUD6A, through upregulation of CDC6, promotes the proliferation of multiple types of human tumour cells in vitro and tumour growth in vivo, suggesting the importance of OTUD6A-CDC6 axis in these cancer cells."
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OTUD6A affects Carcinogenesis
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OTUD6A activates Carcinogenesis.
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"Correction to: Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc."
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"OTUD6A deubiquitinates Brg1 and AR to promote PCa progression, and knockdown of OTUD6A suppresses prostate tumorigenesis by reversing Myc-driven metabolic remodelling [24, 50]."
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"To analyse the progress of bladder tumorigenesis induced by BBN and the protein levels of OTUD6A and CDC6 during the progress, randomly selected mice were sacrificed at the indicated time."
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"OTUD6A specifically promotes prostate tumorigenesis by stabilizing Brg1, AR, and c-Myc through the removal of Brg1, AR, and c-Myc polyubiquitination, respectively [37,38]."
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"OTUD6A promotes prostate tumorigenesis via deubiquitinating Brg1 and AR."
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OTUD6A inhibits Carcinogenesis.
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"In vivo experiments demonstrated that OTUD6A oligonucleotides markedly suppressed prostate tumorigenesis in Pten PC-/- mice and patient-derived xenograft (PDX) models."
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"Moreover, genetic ablation of OTUD6A efficiently represses prostatic tumorigenesis of both human PrCa cells and the Hi-Myc transgenic PrCa mice, via reversing the metabolic remodeling caused by c-Myc overexpression in PrCa."
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OTUD6A inhibits innate immune response. 4 / 4
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"OTUD6A Deficiency Enhances Antiviral Innate Immunity In Vivo."
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"Our data revealed that OTUD6A can both inhibit innate immunity and promote inflammatory response, highlighting its importance in accelerating the cellular response to deadly virus or bacterial infections."
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"In this study, we demonstrated that OTUD6A can attenuate the anti-virus innate immunity response and promote inflammation response.Our findings demonstrate that overexpression of OTUD6A led to the downregulation of Ifnβ expression induced by RIG-I/MAVS, cGAS/STING, TBK1/IRF3, or TRIF overexpression."
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"OTUD6A Deficiency Enhances Antiviral Innate Immunity In Vitro."
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"In vitro experiments demonstrated that the absence of OTUD6A enhanced innate immunity."
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OTUD6A affects Interferon
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OTUD6A inhibits Interferon.
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OTUD6A inhibits Interferon. 3 / 3
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"OTUD6A Overexpression Inhibits the Production of Type I IFN."
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"In this study, we found that OTUD6A significantly inhibited the production of type I interferon."
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"In this study , we found that OTUD6A significantly inhibited the production of type I interferon ."
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OTUD6A decreases the amount of Interferon.
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OTUD6A decreases the amount of Interferon. 1 / 1
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"As hypothesized, overexpression of OTUD6A led to significant inhibition of Ifnβ expression following infection with any of these viruses (Figure 1c), thus confirming its negative regulatory role in the expression of Ifnβ."
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OTUD6A activates Interferon.
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OTUD6A activates Interferon. 1 / 1
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"Furthermore, we collected blood from mice infected with the virus for different days and found that Otud6a−/− mice produced more type I interferon and stronger antiviral-related factors (Ifnβ, Ifit1, Ifit2, and Cxcl10) compared to wild-type mice (Figure 3c)."
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OTUD6A affects gemcitabine
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OTUD6A inhibits gemcitabine.
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OTUD6A inhibits gemcitabine. 3 / 3
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"Notably, treatment with the ATR inhibitor VE-821 and the Chk1 inhibitor GDC-0575 abrogated the decreased gemcitabine sensitivity induced by overexpression of OTUD6A in UMUC3 cells (Fig. 6j, k and Supplementary Fig. 10o-q)."
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"Notably, ectopic expression of CDC6 rescued the hypersensitivity to gemcitabine, methotrexate and HU caused by OTUD6A knockdown (Fig. 6l, m, Supplementary Fig. 10c, d and Supplementary Fig. 12a-e)."
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"Consistent with the observation from in vitro experiments, overexpression of CDC6 rescued the increased chemosensitivity caused by OTUD6A knockdown in gemcitabine-treated T24 tumours (Fig. 6u, v and Supplementary Fig. 12p, q)."
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OTUD6A activates gemcitabine.
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OTUD6A activates gemcitabine. 1 / 1
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"In contrast, OTUD6A overexpression increased the chemoresistance of UMUC3 cells to gemcitabine and methotrexate (Supplementary Fig. 10e, f)."
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OTUD6A affects NLRP3
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OTUD6A binds NLRP3.
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OTUD6A binds NLRP3 and NACHT domain. 1 / 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
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OTUD6A binds NLRP3 and K48. 1 / 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
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OTUD6A binds NLRP3. 1 / 1
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"These findings are consistent with the work of Xin Liu et al. [ xref ], which showed that OTUD6A directly bound to the NACHT domain of the NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased Il1β levels and inflammation [ xref ]."
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OTUD6A deubiquitinates NLRP3.
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OTUD6A deubiquitinates NLRP3. 1 / 1
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"Deubiquitinase OTUD6A in macrophages promotes intestinal inflammation and colitis via deubiquitination of NLRP3."
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OTUD6A
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OTUD6A translocates to the cytoplasm. 2 / 2
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"Moreover, OTUD6A was localized mainly in nuclei in M- and G1-phase cells and translocated to the cytoplasm in S phase (Fig. 4b and Supplementary Fig. 4m)."
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"Moreover, OTUD6A translocates into the cytoplasm in the S phase, indicating that the cytoplasmic translocation of OTUD6A permits the degradation of CDC6 and prevents the re-replication of DNA."
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OTUD6A translocates to the cytoplasm. 1 / 1
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"Moreover, OTUD6A translocates into the cytoplasm in the S phase, indicating that the cytoplasmic translocation of OTUD6A permits the degradation of CDC6 and prevents the re-replication of DNA."
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OTUD6A affects TOPBP1
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OTUD6A activates TOPBP1.
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OTUD6A activates TOPBP1. 2 / 2
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"Consistently, knockout of OTUD6A rendered mice hypersensitive to irradiation, shortened survival, and inhibited tumor growth by regulating TopBP1 in xenografted nude mice."
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"Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy."
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OTUD6A deubiquitinates TOPBP1.
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OTUD6A leads to the deubiquitination of TOPBP1. 1 / 1
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"In addition, OTUD6A inhibits TopBP1 ubiquitination by disrupting the interaction between TopBP1 and UBR5 and promotes tumour cell resistance to chemoradiotherapy [51]."
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NLRP3 affects OTUD6A
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OTUD6A binds NLRP3 and NACHT domain. 1 / 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
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OTUD6A binds NLRP3 and K48. 1 / 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
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OTUD6A binds NLRP3. 1 / 1
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"These findings are consistent with the work of Xin Liu et al. [ xref ], which showed that OTUD6A directly bound to the NACHT domain of the NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased Il1β levels and inflammation [ xref ]."
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DNM1L affects OTUD6A
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DNM1L binds OTUD6A. 1 / 3
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"OTUD6A interacts with and deubiquitinates Drp1 to enhance mitochondrial fission [49]."
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Aurora-A affects OTUD6A
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OTUD6A binds Aurora-A. 3 / 3
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"To confirm the interaction between Aurora-A and OTUD6A, we conducted reverse co-immunoprecipitation by pulling down MYC tagged Aurora-A from the transfected HEK293T cell lysate and subsequently immunoblotted SFB tagged OTUD6A with FLAG antibody."
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"As shown in XREF_FIG b, OTUD6A indeed interacted with Aurora-A."
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"OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A."
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UBE2N affects OTUD6A
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OTUD6A binds UBE2N. 1 / 1
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"To elucidate the mechanism by which OTUD6A participates in the immune response, we employed immunoprecipitation (IP) and mass spectrometry (MS) to enrich and identify potential interacting proteins of OTUD6A. Our results revealed that OTUD6A could interact with UBC13, and further verification experiments demonstrated that this interaction was partly dependent on the N-terminal of OTUD6A."
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OTUD6A binds UBE2N. 1 / 1
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"Immunoprecipitation analysis confirmed that the interaction between OTUD6A and UBC13 was present in the resting state and significantly enhanced after HSV-1 stimulation (Figure 5d)."
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PPP2 affects OTUD6A
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PPP2 dephosphorylates OTUD6A.
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PPP2 dephosphorylates OTUD6A. 1 / 1
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"Mechanistically, in response to DNA damage, the abundance of OTUD6A was increased; meanwhile, PP2A interacted with OTUD6A and dephosphorylated OTUD6A at sites S70/71/74, which promoted nuclear localization of OTUD6A."
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PPP2 binds OTUD6A.
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PPP2 binds OTUD6A. 1 / 1
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"Mechanistically, in response to DNA damage, the abundance of OTUD6A was increased; meanwhile, PP2A interacted with OTUD6A and dephosphorylated OTUD6A at sites S70/71/74, which promoted nuclear localization of OTUD6A."
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OTUD6A affects protein half-life Aurora-A
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OTUD6A activates protein half-life Aurora-A. 2 / 2
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"When normalized following quantitation , the protein half-life of Aurora-A was improved from ~ 17 to ~ 33 h by OTUD6A ( Figure 4a , b ) ."
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"Notably , OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A ."
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"In the context of human colorectal cancer, low expression of OTUD6A leads to suppressed mitochondrial fission and reduced cell growth of proliferating cells ."
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OTUD6A activates mitochondrial fission.
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OTUD6A bound to DNM1L activates mitochondrial fission. 1 / 1
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"OTUD6A interacts with and deubiquitinates Drp1 to enhance mitochondrial fission [49]."
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OTUD6A affects methotrexate
| 2
OTUD6A inhibits methotrexate.
| 1
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"Notably, ectopic expression of CDC6 rescued the hypersensitivity to gemcitabine, methotrexate and HU caused by OTUD6A knockdown (Fig. 6l, m, Supplementary Fig. 10c, d and Supplementary Fig. 12a-e)."
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OTUD6A activates methotrexate.
| 1
OTUD6A activates methotrexate. 1 / 1
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"In contrast, OTUD6A overexpression increased the chemoresistance of UMUC3 cells to gemcitabine and methotrexate (Supplementary Fig. 10e, f)."
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reach
"OTUD6A Deficiency Attenuates the Inflammatory Response In Vitro and In Vivo."
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"A recent study showed that OTUD6A can promote inflammation response during tumorigenesis [42]."
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OTUD6A affects cell growth
| 2
Modified OTUD6A activates cell growth. 1 / 1
| 1
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"Conversely, overexpression of OTUD6A increases Drp1 levels and its protein half-life and enhances cancer cell growth."
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OTUD6A activates cell growth. 1 / 1
| 1
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"In the context of human colorectal cancer, low expression of OTUD6A leads to suppressed mitochondrial fission and reduced cell growth of proliferating cells ."
40328871
OTUD6A affects UBE2N
| 1 1
OTUD6A binds UBE2N. 1 / 1
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"To elucidate the mechanism by which OTUD6A participates in the immune response, we employed immunoprecipitation (IP) and mass spectrometry (MS) to enrich and identify potential interacting proteins of OTUD6A. Our results revealed that OTUD6A could interact with UBC13, and further verification experiments demonstrated that this interaction was partly dependent on the N-terminal of OTUD6A."
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OTUD6A binds UBE2N. 1 / 1
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"Immunoprecipitation analysis confirmed that the interaction between OTUD6A and UBC13 was present in the resting state and significantly enhanced after HSV-1 stimulation (Figure 5d)."
37632103
OTUD6A affects SMARCA4
| 2
OTUD6A deubiquitinates SMARCA4.
| 1
OTUD6A deubiquitinates SMARCA4. 1 / 1
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"OTUD6A deubiquitinates Brg1 and AR to promote PCa progression, and knockdown of OTUD6A suppresses prostate tumorigenesis by reversing Myc-driven metabolic remodelling [24, 50]."
38685067
OTUD6A activates SMARCA4.
| 1
OTUD6A activates SMARCA4. 1 / 1
| 1
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"OTUD6A specifically promotes prostate tumorigenesis by stabilizing Brg1, AR, and c-Myc through the removal of Brg1, AR, and c-Myc polyubiquitination, respectively [37,38]."
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OTUD6A affects PLK1
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OTUD6A activates PLK1. 2 / 2
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"Consequently, our data suggest that Aurora-A, a critical mitotic regulator, is deubiquitinated, stabilized, and activated by OTUD6A, which in turn activates PLK1 to drive cells into mitosis."
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"Consequently , our data suggest that Aurora-A , a critical mitotic regulator , is deubiquitinated , stabilized , and activated by OTUD6A , which in turn activates PLK1 to drive cells into mitosis ."
33669244
OTUD6A affects MYC
| 2
OTUD6A inhibits MYC.
| 1
OTUD6A inhibits MYC. 1 / 1
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"OTUD6A deubiquitinates Brg1 and AR to promote PCa progression, and knockdown of OTUD6A suppresses prostate tumorigenesis by reversing Myc-driven metabolic remodelling [24, 50]."
38685067
OTUD6A activates MYC.
| 1
OTUD6A activates MYC. 1 / 1
| 1
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"OTUD6A specifically promotes prostate tumorigenesis by stabilizing Brg1, AR, and c-Myc through the removal of Brg1, AR, and c-Myc polyubiquitination, respectively [37,38]."
37632103
OTUD6A affects CKS2
| 2
OTUD6A increases the amount of CKS2.
| 1
OTUD6A increases the amount of CKS2. 1 / 1
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"OTUD6A Promotes CKS2 Gene Expression."
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OTUD6A activates CKS2.
| 1
OTUD6A activates CKS2. 1 / 1
| 1
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"We conducted an independent validation and found that CKS2 was significantly upregulated by OTUD6A overexpression (XREF_FIG b)."
33669244
OTUD6A affects CHEK1
| 2
OTUD6A phosphorylates CHEK1.
| 1
OTUD6A leads to the phosphorylation of CHEK1. 1 / 1
| 1
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"Moreover, knockdown of OTUD6A inhibited gemcitabine-induced ATR and Chk1 phosphorylation (Supplementary Fig. 10n)."
38685067
OTUD6A inhibits CHEK1.
| 1
OTUD6A inhibits CHEK1. 1 / 1
| 1
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"Similar to that of OTUD6A overexpression, CDC6 overexpression decreased the chemosensitivity and promoted gemcitabine-induced ATR and Chk1 activation in UMUC3 cells (Supplementary Fig. 11g-k)."
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OTUD6A affects BLNK
| 2
OTUD6A inhibits BLNK. 2 / 2
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"Together, these data indicated that OTUD6A decreases the chemosensitivity of BCa cells."
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reach
"Knockdown of OTUD6A increased but overexpression of OTUD6A decreased the sensitivity of BCa cells to HU (Fig. 6g, h and Supplementary Fig. 10g, h)."
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OTUD6A affects AR
| 2
OTUD6A deubiquitinates AR.
| 1
OTUD6A deubiquitinates AR. 1 / 1
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"OTUD6A deubiquitinates Brg1 and AR to promote PCa progression, and knockdown of OTUD6A suppresses prostate tumorigenesis by reversing Myc-driven metabolic remodelling [24, 50]."
38685067
OTUD6A activates AR.
| 1
OTUD6A activates AR. 1 / 1
| 1
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"OTUD6A specifically promotes prostate tumorigenesis by stabilizing Brg1, AR, and c-Myc through the removal of Brg1, AR, and c-Myc polyubiquitination, respectively [37,38]."
37632103
S70/71/74 affects OTUD6A
| 1
S70/71/74 activates OTUD6A. 1 / 1
| 1
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"Mechanistically, in response to DNA damage, the abundance of OTUD6A was increased; meanwhile, PP2A interacted with OTUD6A and dephosphorylated OTUD6A at sites S70/71/74, which promoted nuclear localization of OTUD6A."
35768646
OTUD6A affects transcription oncogenic cell cycle-regulating
| 1
OTUD6A activates transcription oncogenic cell cycle-regulating. 1 / 1
| 1
eidos
"Moreover , OTUD6A induces the transcription of an oncogenic cell cycle-regulating gene , CKS2 ( Cyclin-dependent kinases regulatory subunit 2 ) [ 24 ] ."
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OTUD6A activates signal transduction. 1 / 1
| 1
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"Taken together, these data demonstrated that OTUD6A promotes CDC6-ATR-Chk1 signalling pathway activity to confer chemoresistance on tumour cells."
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OTUD6A affects protein crucial inducers
| 1
OTUD6A activates protein crucial inducers. 1 / 1
| 1
eidos
"However , it has been demonstrated that OTUD6A enhances the protein levels of one of the crucial EMT inducers , Snail [ 22 ] , and promotes colorectal cancer by deubiquitinating and stabilizing DRP1 [ 23 ] ."
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OTUD6A affects protein Snail epithelial-mesenchymal transition inducer tumorigenecity
| 1
OTUD6A activates protein Snail epithelial-mesenchymal transition inducer tumorigenecity. 1 / 1
| 1
eidos
"OTUD6A enhances the protein levels of Snail , an EMT ( epithelial-mesenchymal transition ) inducer [ 22 ] , and promotes tumorigenecity by deubiquitinating and stabilizing Drp1 [ 23 ] ."
33669244
OTUD6A affects prostatic tumorigenesis
| 1
OTUD6A activates prostatic tumorigenesis. 1 / 1
| 1
eidos
"These results indicate that OTUD6A is a physiological DUB for c-Myc in PrCa setting and specifically promotes prostatic tumorigenesis through stabilizing c-Myc oncoprotein , suggesting that OTUD6A could be a unique therapeutic target for Myc-driven PrCa ."
35217790
OTUD6A affects prostate tumorigenesis
| 1
OTUD6A activates prostate tumorigenesis. 1 / 1
| 1
eidos
"OTUD6A promotes prostate tumorigenesis via deubiquitinating Brg1 and AR ."
35233061
OTUD6A affects kinase Aurora-A
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OTUD6A activates kinase Aurora-A. 1 / 1
| 1
eidos
"We examined whether OTUD6A promotes the kinase activity of Aurora-A by analyzing phosphorylation at threonine 288 ."
33669244
OTUD6A affects hypersensitivity
| 1
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"Knockdown of OTUD6A caused hypersensitivity to gemcitabine and methotrexate in different cancer cell lines detected (Fig. 6a, b and Supplementary Fig. 10a-d)."
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OTUD6A activates epithelial to mesenchymal transition. 1 / 1
| 1
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"However, it has been demonstrated that OTUD6A enhances the protein levels of one of the crucial EMT inducers, Snail [XREF_BIBR], and promotes colorectal cancer by deubiquitinating and stabilizing DRP1 [XREF_BIBR]."
33669244
OTUD6A affects enzymatic
| 1
OTUD6A activates enzymatic. 1 / 1
| 1
eidos
"Collectively , OTUD6A stabilizes Aurora-A and activates its enzymatic activity ."
33669244
OTUD6A affects dextran sulfate
| 1
eidos
"Our data show that OTUD6A deficiency attenuated DSS or TNBS-induced colitis , as well as AOM / DSS-induced colitis-related colon cancer in vivo ."
36932155
OTUD6A affects deubiquitination Aurora-A
| 1
OTUD6A activates deubiquitination Aurora-A. 1 / 1
| 1
eidos
"Only OTUD1 and OTUD6A induced the deubiquitination of Aurora-A ( Figure 2a ) ."
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OTUD6A affects cell cycle
| 1
OTUD6A activates cell cycle. 1 / 1
| 1
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"OTUD6A depletion impaired CHK1 S345 phosphorylation and blocked cell cycle progression under DNA replication stress."
35768646
OTUD6A affects Supplementary Fig. 6i-k
| 1
OTUD6A activates Supplementary Fig. 6i-k. 1 / 1
| 1
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"Knockdown of OTUD6A in T24 and 786-O cells significantly inhibited tumour growth (Fig. 5h-j and Supplementary Fig. 6i-k)."
38685067
OTUD6A affects Supplementary Fig. 11g-k
| 1
OTUD6A inhibits Supplementary Fig. 11g-k. 1 / 1
| 1
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"Similar to that of OTUD6A overexpression, CDC6 overexpression decreased the chemosensitivity and promoted gemcitabine-induced ATR and Chk1 activation in UMUC3 cells (Supplementary Fig. 11g-k)."
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OTUD6A affects STAT3
| 1
OTUD6A activates STAT3. 1 / 1
| 1
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"OTUD6A in tubular epithelial cells mediates Angiotensin II-induced kidney injury by targeting STAT3."
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OTUD6A affects SNAI1
| 1
OTUD6A increases the amount of SNAI1. 1 / 1
| 1
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"OTUD6A enhances the protein levels of Snail, an EMT (epithelial-mesenchymal transition) inducer [XREF_BIBR], and promotes tumorigenecity by deubiquitinating and stabilizing Drp1 [XREF_BIBR]."
33669244
OTUD6A affects Protein Stability Kinase Aurora-A
| 1
OTUD6A activates Protein Stability Kinase Aurora-A. 1 / 1
| 1
eidos
"OTUD6A Promotes Protein Stability and Kinase Activity of Aurora-A To determine whether OTUD6A-mediated deubiquitination increases protein stability of Aurora-A , we transfected SFB-tagged OTUD6A into HEK293T cells and treated the cells with cycloheximide at 50 mug / mL for the indicated period ."
33669244
OTUD6A affects PPP2
| 1
PPP2 binds OTUD6A. 1 / 1
| 1
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"Mechanistically, in response to DNA damage, the abundance of OTUD6A was increased; meanwhile, PP2A interacted with OTUD6A and dephosphorylated OTUD6A at sites S70/71/74, which promoted nuclear localization of OTUD6A."
35768646
OTUD6A affects OTUD6A-CDC6
| 1
OTUD6A activates OTUD6A-CDC6. 1 / 1
| 1
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"We further showed that OTUD6A, through upregulation of CDC6, promotes the proliferation of multiple types of human tumour cells in vitro and tumour growth in vivo, suggesting the importance of OTUD6A-CDC6 axis in these cancer cells."
38685067
OTUD6A affects Neoplasms
| 1
OTUD6A activates Neoplasms. 1 / 1
| 1
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"Consistently, knockout of OTUD6A rendered mice hypersensitive to irradiation, shortened survival, and inhibited tumor growth by regulating TopBP1 in xenografted nude mice."
35768646
OTUD6A affects NACHT domain
| 1
OTUD6A binds NLRP3 and NACHT domain. 1 / 1
| 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
36932155
OTUD6A affects Mice
| 1
OTUD6A inhibits Mice. 1 / 1
| 1
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"Moreover, genetic ablation of OTUD6A efficiently represses prostatic tumorigenesis of both human PrCa cells and the Hi-Myc transgenic PrCa mice, via reversing the metabolic remodeling caused by c-Myc overexpression in PrCa."
35217790
OTUD6A affects MCM7
| 1
OTUD6A inhibits MCM7. 1 / 1
| 1
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"Importantly, ectopic expression of CDC6 effectively reduced the defects in cell proliferation of cancer cells and restored the decreased level of chromatin-bound MCM2 in vitro caused by OTUD6A knockdown (Fig. 5l-n, Supplementary Fig. 7l and Supplementary Fig. 8a-l)."
38685067
OTUD6A affects K48
| 1
OTUD6A binds NLRP3 and K48. 1 / 1
| 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
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eidos
"Moreover , OTUD6A is expressed at high levels in breast cancer , and OTUD6A overexpression promotes cell proliferation , migration and invasion , indicating that dysregulation of OTUD6A expression contributes to genomic instability and is associated with tumor development ."
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OTUD6A affects Fibrosis
| 1
OTUD6A inhibits Fibrosis. 1 / 1
| 1
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"Moreover, OTUD6A deficiency significantly protected mice against Ang II-induced kidney dysfunction and fibrosis."
38105755
OTUD6A affects DNA repair
| 1
OTUD6A activates DNA repair. 1 / 1
| 1
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"We next assessed the role of OTUD6A in DNA replication reinitiation after HU treatment, and the results showed that the DNA replication reinitiation rate was decreased in OTUD6A-knockdown T24 cells after release from HU (Fig. 6i and Supplementary Fig. 10j), suggesting that inhibition of OTUD6A increases DNA damage and reduces DNA repair caused by HU in BCa cells.The ATR-Chk1 pathway is a key signalling axis driving the DDR [2], and CDC6 has been identified as a critical regulator of ATR-Chk1 activation [2, 8, 9, 42]."
38685067
OTUD6A affects DNA Damage
| 1
OTUD6A inhibits DNA Damage. 1 / 1
| 1
reach
"We next assessed the role of OTUD6A in DNA replication reinitiation after HU treatment, and the results showed that the DNA replication reinitiation rate was decreased in OTUD6A-knockdown T24 cells after release from HU (Fig. 6i and Supplementary Fig. 10j), suggesting that inhibition of OTUD6A increases DNA damage and reduces DNA repair caused by HU in BCa cells.The ATR-Chk1 pathway is a key signalling axis driving the DDR [2], and CDC6 has been identified as a critical regulator of ATR-Chk1 activation [2, 8, 9, 42]."
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OTUD6A activates Colorectal Neoplasms. 1 / 1
| 1
eidos
"However , it has been demonstrated that OTUD6A enhances the protein levels of one of the crucial EMT inducers , Snail [ 22 ] , and promotes colorectal cancer by deubiquitinating and stabilizing DRP1 [ 23 ] ."
33669244
OTUD6A affects CDC6-ATR-Chk1
| 1
OTUD6A activates CDC6-ATR-Chk1. 1 / 1
| 1
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"Taken together, these data demonstrated that OTUD6A promotes CDC6-ATR-Chk1 signalling pathway activity to confer chemoresistance on tumour cells."
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OTUD6A affects ATR
| 1
OTUD6A leads to the phosphorylation of ATR. 1 / 1
| 1
reach
"Moreover, knockdown of OTUD6A inhibited gemcitabine-induced ATR and Chk1 phosphorylation (Supplementary Fig. 10n)."
38685067
OTUD1 affects OTUD6A
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OTUD1 activates OTUD6A. 1 / 1
| 1
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"Moreover, OTUD1 was not able to increase the enzymatic activity of Aurora-A as much as OTUD6A."
33669244
NLRP3 affects NACHT domain
| 1
OTUD6A binds NLRP3 and NACHT domain. 1 / 1
| 1
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"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
36932155
NLRP3 affects K48
| 1
OTUD6A binds NLRP3 and K48. 1 / 1
| 1
reach
"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
36932155
NACHT domain affects OTUD6A
| 1
OTUD6A binds NLRP3 and NACHT domain. 1 / 1
| 1
reach
"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
36932155
K48 affects OTUD6A
| 1
OTUD6A binds NLRP3 and K48. 1 / 1
| 1
reach
"Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation."
36932155
BLNK affects OTUD6A
| 1
BLNK activates OTUD6A. 1 / 1
| 1
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"Our results confirmed the synergistic effect of ATR/Chk1 inhibitors and gemcitabine in OTUD6A-overexpressing BCa cells, suggesting the possible beneficial effects of targeting ATR/Chk1 in cancers with high expression of OTUD6A and CDC6."
38685067
Angiotensin-2 affects OTUD6A
| 1
Angiotensin-2 activates OTUD6A. 1 / 1
| 1
reach
"These studies identified STAT3 as a direct substrate of OTUD6A and highlighted the pivotal role of OTUD6A in Ang II-induced kidney injury, indicating OTUD6A as a potential therapeutic target for HKD."
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