Molecular Cancer Research and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
Nat Commun. 2011;2:316. doi: 10.1038/ncomms1319.
The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis.
有丝分裂检查点防止有丝分裂末期的发生，直到所有染色体都与纺锤体微管连接。极光激酶 B 通过使错误的连接不稳定间接地引发这个检查点；然而，一个更直接的作用仍然存在争议。相比之下，激酶 Mps1 的活性对于有丝分裂检查点是必不可少的。在这里，我们发现 Aurora B 和 Hec1 对于有效招募 Mps1 到未连接的动粒是必需的，这使得 Mps1 在有丝分裂开始时能够迅速被激活。对细胞周期蛋白 B 降解的实时监测表明，这对于在有丝分裂开始时快速建立有丝分裂检查点是必不可少的。在抑制 Aurora B 或耗尽 Hec1 后，Mps1 与动粒的连接挽救了 Mps1 的延迟激活和检查点的建立，这表明 Mps1 的募集是 Aurora B 和 Hec1 在有丝分裂检查点信号中的主要作用。这些数据表明 Aurora B 在有丝分裂开始时迅速引发有丝分裂检查点的直接作用。
