IndraLab

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USP10 inhibits MYC. 19 / 23
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"Third, USP10 antagonizes c-Myc transcriptional activity and cell cycle progression through both SIRT6 and p53."
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"Consistent with these discoveries, we demonstrated that p53 is also involved in USP10 mediated c-Myc suppression, as ectopic USP10 expression partially inhibited c-Myc activity in cancer cells."
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"Expression of USP10 significantly suppressed c-Myc transcriptional activity in p53 wildtype and p53 -/- HCT116 cells, but the levels of USP10 mediated suppression in c-Myc target gene transcription in p53-null cells were partially reversed."
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"These results indicate that p53 is downstream of USP10 in suppressing c-Myc transcriptional activity, but additional factors, one of which presumably is SIRT6 as indicated from our results in XREF_FIG, are involved in USP10 mediated c-Myc suppression."
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"In human colon cancer, USP10 and SIRT6 protein expressions were reduced, and USP10 antagonized c-Myc transcriptional activity through SIRT6 and p53 to inhibit cell cycle progression, cancer cell growth, and tumor formation [XREF_BIBR]."
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"To further prove the principle that USP10 suppresses c-Myc transcriptional activity through both SIRT6 and p53, we tested whether knockdown of SIRT6 rescues this USP10 suppressive activity."
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"Interaction of USP10 and SIRT6 suppresses tumor cell growth by p53-mediated suppression of the oncogene c-Myc [ 4 ]."
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"We then used SIRT6-null mouse embryonic fibroblasts (MEFs) to prove the principle that SIRT6 is another downstream factor in USP10 mediated c-Myc suppression."
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"Conversely, expression of USP10 significantly suppressed c-Myc target gene transcription both in wildtype MEFs, and the USP10 suppressive activity of c-Myc target gene expression was partially reversed in SIRT6 -/- MEFs (XREF_FIG), further suggesting that other factors, such as p53, are involved in USP10 mediated c-Myc suppression."
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"In addition, p53 knockdown partially abolished USP10 over-expression-mediated suppression in c-Myc target gene expression in SIRT6 +/+ MEFs, and p53 knockdown in SIRT6 -/- MEFs fully reversed USP10 mediated suppression of c-Myc targets expression (XREF_FIG)."
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"USP10 inhibits c-Myc transcriptional activity."
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"Therefore, USP10 might antagonize c-Myc activity to inhibit tumor cell growth though SIRT6 and p53."
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"We then reasoned that, if USP10 suppresses c-Myc transcriptional activity through SIRT6 stabilization, knockdown of SIRT6 expression should achieve a similar level of increase in c-Myc target gene expression in human colon cancer cells."
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"Previous studies have shown that USP10 antagonizes c-Myc transcriptional activation that could promote Sirt6 stabilization to suppress tumor formation."
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"We then used in vitro anchorage independent colony formation assay and analyzed the role of USP10 mediated c-Myc suppression in tumor formation."
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"Collectively, our results indicate that USP10 suppresses c-Myc transcriptional activity partially through SIRT6."
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"USP10 suppresses c-Myc transcriptional activity through SIRT6 and p53."
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"Our results in XREF_FIG imply that additional factors are involved in USP10 mediated c-Myc suppression."
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"It has been reported that one of the molecular mechanisms underlying USP10 tumor-suppressive functions is that it protects p53 from degradation, raising the possibility that USP10 also antagonizes c-Myc transcriptional activity through p53."
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