Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation
Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation
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DOI：
10.1126/science.1148980
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发表时间：
2008-01-25
期刊：
影响因子：
56.9
通讯作者：
Stukenberg, P. Todd
中科院分区：
文献类型：
--
作者：
Rosasco-Nitcher, Sara E.;Lan, Weijie;Stukenberg, P. Todd
染色体乘客复合体(CPC)在有丝分裂过程中控制着染色体聚集、着丝粒-微管附着和纺锤体检查点信号传递。极光B激酶是CPC的催化亚单位。为了了解单个激酶如何调节这些不同的事件，我们研究了Aurora-B的激活，并描述了两种不同的激活机制。首先，Aurora-B的体外激活需要两个辅助因子，端粒盘-60kD(TD-60)和微管。TD-60对于将CPC和Haspin Kinase活性定位到着丝粒，从而在多个水平上调节Aurora-B至关重要。其次，Aurora-B底物可以抑制激酶的激活，这可以通过着丝粒激酶Plk1和Haspin对这些底物的磷酸化而缓解。这些调节机制提出了Aurora-B对未对齐的染色体和分生组织连接的着丝粒底物进行磷酸化的模型。
The chromosome passenger complex ( CPC) controls chromosome congression, kinetochore- microtubule attachments, and spindle checkpoint signaling during mitosis. Aurora- B kinase is the catalytic subunit of the CPC. To understand how a single kinase can regulate such diverse events, we have investigated the activation of Aurora- B and describe two distinct activation mechanisms. First, Aurora- B activation in vitro requires two cofactors, telophase disc-60kD ( TD-60) and microtubules. TD-60 is critical to localize both the CPC and Haspin kinase activity to centromeres and thus regulates Aurora- B at several levels. Second, Aurora- B substrates can inhibit kinase activation, and this is relieved by phosphorylation of these substrates by the centromeric kinases Plk1 and Haspin. These regulatory mechanisms suggest models for phosphorylation by Aurora- B of centromeric substrates at unaligned chromosomes and merotelic attachments.