Department of Medical Oncology, University Medical Center Utrecht, Universiteitsweg 100, STR 2.129, 3584 CG Utrecht, The Netherlands.
EMBO Rep. 2012 Sep;13(9):847-54. doi: 10.1038/embor.2012.93. Epub 2012 Jun 26.
Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimulates the latter recruitment axis. Mps1 activity enhances H2A-T120ph and is critical for Sgo1 recruitment to centromeres, thereby promoting Aurora B centromere recruitment in early mitosis. Importantly, chromosome biorientation defects caused by Mps1 inhibition are improved by restoring Aurora B centromere recruitment. As Mps1 kinetochore localization reciprocally depends on Aurora B, we propose that this Aurora B-Mps1 recruitment circuitry cooperates with the Aurora B-Haspin feedback loop to ensure rapid centromere accumulation of Aurora B at the onset of mitosis.
极光 B 向有丝分裂着丝粒的定位，这是有丝分裂过程中正确染色体排列所必需的，依赖于 Haspin 依赖性组蛋白 H3 磷酸化和 Bub1 依赖性组蛋白 H2A 磷酸化，这些磷酸化与通过 Shugoshin（Sgo）中间物与 Borealin 相互作用。我们证明 Mps1 刺激了后一个募集轴。Mps1 活性增强 H2A-T120ph，对 Sgo1 向着丝粒的募集至关重要，从而促进早期有丝分裂中极光 B 向着丝粒的募集。重要的是，通过恢复极光 B 着丝粒募集可以改善 Mps1 抑制引起的染色体双定向缺陷。由于 Mps1 动粒定位与极光 B 相互依赖，我们提出这种极光 B-Mps1 募集电路与极光 B-Haspin 反馈环合作，以确保在有丝分裂开始时快速积累极光 B 到着丝粒。
