IndraLab

Statements


OTUB1 increases the amount of MDM4.
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OTUB1 increases the amount of MDM4. 6 / 6
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"Consequently, overexpression of Otub1 markedly stabilized MDMX and increased its levels, whereas knockdown of Otub1 reduced the levels of MDMX."

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"Overexpression of Otub1 markedly stabilized MDMX and induced its levels, whereas knockdown of Otub1 reduced the levels of MDMX."

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"Doxycycline induced expression of Otub1 in T-Rex-U2OS-Flag-Otub1 cells also drastically induced the levels of MDMX, as well as p53 and its target MDM2 in a time dependent manner."

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"Consistently, knockdown of endogenous Otub1 by two different siRNAs significantly reduced the levels of MDMX in cells."

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"These results suggest that Otub1 increases the cytoplasmic levels of both MDMX and p53."

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"The authors later showed OTUB1 also increases MDMX protein levels through a similar mechanism, which facilitates P53 activation (Chen et al., 2017) (Figure 5B)."
Modified OTUB1 increases the amount of MDM4. 1 / 1
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"As shown in Figure XREF_FIG, cell fractionation assays revealed that Otub1 expression not only significantly induced the nuclear levels of p53 and MDMX, but also induced the levels of cytoplasmic MDMX and p53 (lane 4, Figure XREF_FIG)."
OTUB1 activates MDM4.
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OTUB1 activates MDM4. 3 / 3
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"Interestingly, MDMX induced by Otub1 can localize to mitochondria in addition to the cytosol, enhance p53 phosphorylation at S46 (p53S46P) and promote mitochondria mediated apoptotic pathway."

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"Also, induced overexpression of Otub1 drastically prolonged the half-life of MDMX as determined by half-life assays."

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"Together, these results suggest that Otub1 also induces mitochondrial mediated apoptosis by stabilizing MDMX and relocalizing it to mitochondria to induce mitochondria mediated apoptosis."
OTUB1 binds MDM4.
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"It deubiquitinates and stabilizes mitochondrial respiratory chain complex I subunit NDUFS2 (NADH:ubiquinone oxidoreductase core subunit S2) to suppress apoptosis in pancreatic cancer cells, xref whereas its enzyme-independent stabilization of MDMX enhances phosphorylation of p53 at serine 46 (p53S46P), promoting the mitochondrial apoptosis pathway. xref This effect is mechanistically distinct from MDM2-mediated p53 degradation: rather than influencing p53 protein stability, OTUB1-MDMX interaction modulates p53 PTM and activity."