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OTUD1 deubiquitinates STAT3. 7 / 7
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"Mechanistically, OTUD1 bounds to the SH2 domain of STAT3 and causes deubiquitination of STAT3."
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"Finally, OTUD1 overexpression by AAV9 vector increases Ang II-induced cardiac remodeling in mice and OTUD1-regulated responses can be inhibited by blocking STAT3.Conclusion: Cardiomyocyte OTUD1 promotes pathological cardiac remodeling and dysfunction by deubiquitinating STAT3."
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"From this setup, we show that OTUD1 reduces the ubiquitination of STAT3 (Figure 6A)."
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"The authors found that OTUD1 deubiquitinates and stabilizes STAT3, thereby enhancing its activity and contributing to adverse cardiac remodeling and dysfunction 57."
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"For example, OTUD1 affects the inflammatory response by deubiquitinating the STAT3 gene and influences pro-inflammatory cytokine production by cleaving its ubiquitin chain through direct interaction with CARD9 (Chen et al., 2021); OTUD1 also affects IFN signaling and innate immune response by stabilizing TyK2 protein (Zhang et al., 2022)."
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"Although the involved lysine residues in STAT3 are not identified, this is the first time to present a K63-linked deubiquitination of STAT3 by OTUD1 to regulate STAT3 activity."
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"We mapped SH2 domain on STAT3 as the OTUD1 binding site and showed that OTUD1 deubiquitinates STAT3 to increase p-STAT3 levels and STAT3 nuclear translocation."
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