From the Ministry of Education (MOE) Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
From the Ministry of Education (MOE) Laboratory of Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China
J Biol Chem. 2019 Feb 8;294(6):2021-2035. doi: 10.1074/jbc.RA118.005978. Epub 2018 Dec 6.
The chromosomal passenger complex (CPC) is a master regulator of mitosis. CPC consists of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B and plays key roles in regulating kinetochore-microtubule attachments and spindle assembly checkpoint signaling. However, the role of CPC in sister chromatid cohesion, mediated by the cohesin complex, remains incompletely understood. Here, we show that Aurora B kinase activity contributes to centromeric cohesion protection partly through promoting kinetochore localization of the kinase Bub1. Interestingly, disrupting the interaction of INCENP with heterochromatin protein 1 (HP1) in HeLa cells selectively weakens cohesion at mitotic centromeres without detectably reducing the kinase activity of Aurora B. Thus, through this INCENP-HP1 interaction, the CPC also protects centromeric cohesion independently of Aurora B kinase activity. Moreover, the requirement for the INCENP-HP1 interaction in centromeric cohesion protection can be bypassed by tethering HP1 to centromeres or by depleting the cohesin release factor Wapl. We provide further evidence suggesting that the INCENP-HP1 interaction protects centromeric cohesion by promoting the centromere localization of Haspin, a protein kinase that antagonizes Wapl activity at centromeres. Taken together, this study identifies Aurora B kinase activity-dependent and -independent roles for the CPC in regulating centromeric cohesion during mitosis in human cells.
染色体乘客复合物（CPC）是有丝分裂的主要调节剂。CPC 由着丝粒蛋白（INCENP）、Survivin、Borealin 和激酶 Aurora B 组成，在调节动粒微管附着和纺锤体组装检查点信号方面发挥着关键作用。然而，CPC 在姐妹染色单体黏合中的作用，由着丝粒复合物介导，仍然不完全清楚。在这里，我们表明 Aurora B 激酶活性有助于着丝粒黏合的保护，部分原因是通过促进激酶 Bub1 在动粒上的定位。有趣的是，在 HeLa 细胞中破坏 INCENP 与异染色质蛋白 1（HP1）的相互作用，选择性地削弱有丝分裂着丝粒处的黏合，而不会明显降低 Aurora B 的激酶活性。因此，通过这种 INCENP-HP1 相互作用，CPC 也可以独立于 Aurora B 激酶活性来保护着丝粒黏合。此外，将 HP1 固定在着丝粒上或耗尽着丝粒释放因子 Wapl 可以绕过 CPC 中 INCENP-HP1 相互作用在保护着丝粒黏合中的需求。我们提供了进一步的证据表明，INCENP-HP1 相互作用通过促进 Haspin（一种在着丝粒处拮抗 Wapl 活性的蛋白激酶）在着丝粒上的定位来保护着丝粒黏合。总之，这项研究确定了 CPC 在调节人类细胞有丝分裂期间着丝粒黏合中的 Aurora B 激酶活性依赖性和非依赖性作用。
