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MMSET AURKA Use for regulating cell proliferation and apoptosis by MMSET-mediated methylation of AURKA
MMSET AURKA Use for regulating cell proliferation and apoptosis by MMSET-mediated methylation of AURKA
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机译:MMSET AURKA用于通过MMSET介导的AURKA甲基化调节细胞增殖和凋亡
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摘要
The present invention relates to the use of MMSET-mediated AURKA methylation to regulate cell proliferation and apoptosis. MMSET/WHSC1 is highly expressed in several tumor types, and its expression has been shown to be involved in cell proliferation. The present inventors confirmed that MMSET binds to Aurora kinase A (AURKA) and methylates AURKA. The present inventors confirmed that MMSET-mediated methylation of AURKA induces binding to p53 and enhances the kinase activity of AURKA, which caused proteasome degradation of p53. MMSET-mediated p53 degradation increased cell proliferation and showed oncogenic activity. In addition, the knockout of MMSET strongly inhibited tumorigenic cells, and showed sensitivity to growth inhibition by the therapeutic drug alisertib (AURKA inhibitor). In conclusion, the present invention showed that in proliferating cells, MMSET modulates p53 stability through methylation of AURKA, and may be a potential therapeutic target in solid cancer.
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