Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation.
Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation.
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TIP60 对 Aurora B 进行乙酰化可确保准确的染色体分离
DOI：
10.1038/nchembio.2017
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发表时间：
2016-04
影响因子：
14.8
通讯作者：
Yao X
中科院分区：
文献类型：
--
作者：
Mo F;Zhuang X;Liu X;Yao PY;Qin B;Su Z;Zang J;Wang Z;Zhang J;Dou Z;Tian C;Teng M;Niu L;Hill DL;Fang G;Ding X;Fu C;Yao X
在哺乳动物细胞中，染色体的忠实分离需要姐妹染色单体的双向取向，这依赖于纺锤体微管和动粒之间正确附着的传感。虽然触发有丝分裂进入的细胞周期蛋白依赖性激酶1（CDK 1）激活的潜在机制已被广泛研究，但将CDK 1-细胞周期蛋白B活性与染色体稳定性偶联的调节机制尚未完全了解。在这里，我们确定了一个信号转导轴，其中极光B活性是由CDK 1-细胞周期蛋白B通过乙酰转移酶TIP 60在人类细胞分裂。CDK 1-cyclin B磷酸化TIP 60的Ser 90，从而增强Aurora B的TIP 60依赖性乙酰化，并促进有丝分裂中染色体的精确分离。从机制上讲，Aurora B在Lys 215处的TIP 60乙酰化保护Aurora B的激活环免受磷酸酶PP 2A的去磷酸化，以确保稳健、无错误的中期-后期转换。这些发现描绘了一个保守的信号级联，整合蛋白磷酸化和乙酰化与细胞周期的进展，以维持基因组的稳定性。
Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1–cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1–cyclin B via the acetyltransferase TIP60 in human cell division. CDK1–cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability.