Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis.
Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis.
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DOI：
10.1038/ncomms12059
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发表时间：
2016-07-08
影响因子：
16.6
通讯作者：
Nakanishi M
中科院分区：
文献类型：
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作者：
Shimada M;Goshima T;Matsuo H;Johmura Y;Haruta M;Murata K;Tanaka H;Ikawa M;Nakanishi K;Nakanishi M
在哺乳动物中，着丝粒上极光B的正确沉积和激活对于染色体分离是至关重要的。然而，着丝粒上Aurora B激酶突然激活的机制基础尚未完全了解。我们在这里证明了极光B介导的组蛋白H2AX丝氨酸121位点的磷酸化（H2AX- ps121）促进了极光B的自磷酸化，这对于正确的染色体分离是必不可少的。Aurora b介导的H2AX-pS121在有丝分裂过程中特异性检测到。H2AX耗损导致极光B在该位点的激活和沉积严重缺陷。H2AX在S121位点的磷酸化突变体比野生型更有效地与活化的Aurora B相互作用。综上所述，这些结果提出了一个模型，在这个模型中，Aurora B介导的H2AX-pS121可能为着丝粒上的Aurora B自激活电路提供了一个平台，从而在适当的染色体分离中起关键作用。在哺乳动物中，着丝粒上的极光B激活对忠实的染色体分离至关重要。在这里，作者表明，Aurora B介导的组蛋白H2AX丝氨酸121位点的磷酸化对于着丝粒上Aurora B的自激活回路至关重要，从而确保了正确的染色体分离。
Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation. Aurora B activation at the centromere is critical for faithful chromosome segregation in mammals. Here the authors show that Aurora B-mediated phosphorylation of histone H2AX at serine 121 is essential for Aurora B auto-activation circuitry at centromeres, ensuring proper chromosome segregation.