IndraLab

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BAP1 increases the amount of MYCN. 7 / 7
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"Inhibiting BAP1 by shRNA-mediated knockdown decreases the expression of MYCN largely through reducing the BAP1-mediated deubiquitination of MYCN."
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"Moreover, BAP1, but not OTUD4, upregulated the MYCN protein level in a dose-dependent manner (Supplementary Fig. 1A)."
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"However, further experiment indicated that only BAP1 and USP7 could elevate the MYCN protein level in a dose-dependent manner, but BAP1 have the best effect on the elevation of MYCN protein levels (Fig. 1F)."
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"Therefore, given the better effect of BAP1 in elevating MYCN protein levels in our experimental settings, the BAP1 will be our major focus in the remainder of the study.Next, we performed the protein half-life assay and ubiquitination assay to further confirm whether BAP1 is a bona fide DUB for MYCN to plays a vital role in positively regulating MYCN protein abundance."
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"The results showed that BAP1-WT, but not BAP1-C91S, dramatically elevated the MYCN protein levels (Fig. 1J)."
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"The results indicated that FBXW7 could efficiently promote the degradation of MYCN, but BAP1 could antagonize the degradation effect of FBXW7 and markedly rescued the protein levels of MYCN in a dose-dependent manner (Supplementary Fig. 1C, D)."
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"Hence, our results suggest that the decreased protein levels of MYCN caused by depletion of BAP1 might contribute the resistance to BET inhibitors and Aurora Kinase A inhibitors in NB cells."
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