Department of Biochemistry, University of Oxford, Oxford, UK.
J Cell Biol. 2020 Jul 6;219(7). doi: 10.1083/jcb.201910059.
The Aurora B chromosomal passenger complex (CPC) is a conserved regulator of mitosis. Its functions require localization first to the chromosome arms and then centromeres in mitosis and subsequently the central spindle in anaphase. Here, we analyze the requirements for core CPC subunits, survivin and INCENP, and the mitotic kinesin-like protein 2 (MKLP2) in targeting to these distinct localizations. Centromere recruitment of the CPC requires interaction of survivin with histone H3 phosphorylated at threonine 3, and we provide a complete structure of this assembly. Furthermore, we show that the INCENP RRKKRR-motif is required for both centromeric localization of the CPC in metaphase and MKLP2-dependent transport in anaphase. MKLP2 and DNA bind competitively to this motif, and INCENP T59 phosphorylation acts as a switch preventing MKLP2 binding in metaphase. In anaphase, CPC binding promotes the microtubule-dependent ATPase activity of MKLP2. These results explain how centromere targeting of the CPC in mitosis is coupled to its movement to the central spindle in anaphase.
极光 B 染色体乘客复合物（CPC）是有丝分裂的保守调节剂。其功能首先需要定位到染色体臂，然后在有丝分裂中定位到着丝粒，随后在后期定位到着丝粒纺锤体。在这里，我们分析了核心 CPC 亚基、survivin 和 INCENP 以及有丝分裂驱动蛋白样蛋白 2（MKLP2）在这些不同定位中的靶向要求。CPC 到着丝粒的募集需要 survivin 与 Thr3 磷酸化的组蛋白 H3 相互作用，我们提供了这个组装体的完整结构。此外，我们表明 INCENP 的 RRKKRR 基序对于 CPC 在中期的着丝粒定位和后期依赖于 MKLP2 的运输都是必需的。MKLP2 和 DNA 竞争性地与该基序结合，并且 INCENP T59 磷酸化作为一种开关，防止在中期与 MKLP2 结合。在后期，CPC 结合促进了 MKLP2 的微管依赖性 ATP 酶活性。这些结果解释了有丝分裂中 CPC 到着丝粒的靶向如何与后期到着丝粒纺锤体的运动相偶联。
