IndraLab

Statements

USP9X activates CEP131. 10 / 10
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"Collectively, these observations suggest a potential role for USP9X promoted CEP131 stabilization in breast carcinogenesis."
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"We next asked the question how USP9X promoted CEP131 stabilization has an impact on centrosome biogenesis."
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"In vitro deubiquitination assays revealed that, while USP9X was able to remove ubiquitins of CEP131 and K504R, but not that of CEP131 and K254R (XREF_FIG), favouring the argument that USP9X targets K254 of CEP131 for deubiquitination, although polyubiquitin chains conjugated onto CEP131 and K254R and CEP131 and K504R were both dramatically reduced (XREF_FIG)."
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"Combining the findings that mildly disrupted centrosomal localization of PCM1 has minimal effect on CEP131 recruitment and the observations that USP9X directly interacts with CEP131 and opposes its polyubiquitin linkages in vitro, we get the conclusion that the effect of USP9X on CEP131 stabilization is attributed to the interplay between these two molecules but not through USP9X targeting other substrates like PCM1, and USP9X regulated PCM1 stabilization on centrosome activity, if it does so, seems to be independent of USP9X promoted CEP131 stabilization."
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"On the other hand, Li and colleagues demonstrated that USP9X, a well studied protein with oncogenic potential (Schwickart et al., 2010), promotes CEP131 stabilization through deubiquitination (Li et a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"To gain molecular insights into the functional connection between USP9X and CEP131, we examined whether USP9X promoted CEP131 stabilization is dependent on the enzymatic activity of USP9X."
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"To investigate whether and how other substrates of USP9X might affect the cellular function of USP9X promoted CEP131 stabilization, we analysed by WB analysis the expression of IPO5, PRMT5 and PPM1B, which were also identified as interactors of USP9X (XREF_SUPPLEMENTARY), and the results indicate that the protein abundance of these proteins was essentially unchanged upon USP9X knockdown (XREF_SUPPLEMENTARY)."
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"Since centrosome dysregulation associated mitotic defects could result in genome instability and cell apoptosis XREF_BIBR XREF_BIBR XREF_BIBR, we examined whether USP9X promoted CEP131 stabilization plays a role in genome stability and cell death."
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"These results indicate that USP9X promoted CEP131 stabilization is required for breast cancer cell survival."
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"Together, these results indicate that overexpression of USP9X promotes centrosome amplification and mitotic defects in a CEP131 dependent manner."
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