IndraLab

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OTUD4 deubiquitinates NT5E. 7 / 7
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"Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses."
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"Collectively, these results imply that TGF-β may enhance OTUD4 levels, contributing to the stabilization of CD73.To confirm the role of amino acids V300 and I301 in facilitating the TGF-β–mediated deubiquitylation of CD73 by OTUD4, Figure 4L shows that TGF-β treatment reduced the ubiquitylation level, which in turn stabilized the CD73 protein in MDA-MB-468-CD73 cells."
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"More importantly, we have developed a pharmacologic inhibitor, ST80 that is potent to specifically inhibit the physical interaction of OTUD4 and CD73 to promote ubiquitylation of CD73, thereby causing CD73 degradation and revival of CD8 T cell function."
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"Increased CD73 deubiquitylation by OTUD4 due to etiological factors enhances function for membrane-bound CD73, conferring tumor immune evasion."
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"Interestingly, the deubiquitylation of CD73 by OTUD4 is regulated by TGF-β signalling [113]."
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"This intricate regulatory mechanism governs CD73 abundance on the cell membrane, whereby heightened CD73 deubiquitylation by OTUD4 augments its functionality.In exploring the potential association between increased CD73 expression and reduced immunogenicity in a subset of TNBC, the authors conducted a Cybersort analysis."
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"Therefore, radiotherapy can regulate the deubiquitylation of CD73 by OTUD4 and stabilize CD73 expression by activating the TGF-β signalling pathway.Radiotherapy induces DNA breaks in tumour cells through high-energy ionizing radiation, triggering the apoptosis pathway and thus effectively killing tumour cells."
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