J Biol Chem. 2014 Jul 25;289(30):20638-49. doi: 10.1074/jbc.M114.572842.
Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1 (HP1) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1. This borealin-HP1 interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1 interaction, demonstrating the spatial requirement of HP1 in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1 and CPC localization in the centromere and illustrate the critical role of borealin-HP1 interaction in orchestrating an accurate cell division.
准确的有丝分裂需要包含 Aurora B 激酶、Borealin、INCENP 和 survivin 的染色体乘客蛋白复合物（CPC），该复合物协调染色体动力学。然而，将 CPC 指定到着丝粒的染色质因子仍然难以捉摸。在这里，我们表明 Borealin 与异染色质蛋白 1（HP1）直接相互作用，并且这种相互作用是由 C 末端 Borealin 中的进化上保守的 PXVXL 基序介导的，该基序与 HP1 的染色质阴影结构域相互作用。这种 Borealin-HP1 相互作用将 CPC 募集到着丝粒，并通过 Aurora B 激酶的磷酸化 Ser-7 来判断其激活，Aurora B 激酶是 Aurora B 的底物。一致地，该 motif PXVXL 的调节导致 CPC 着丝粒靶向缺陷和异常的 Aurora B 活性。另一方面，CPC 在中部区域的定位与 Borealin-HP1 相互作用无关，这表明 HP1 在 CPC 定位到着丝粒中的空间要求。这些发现揭示了 HP1 和 CPC 在着丝粒中的定位之间以前未被认识但直接的联系，并说明了 Borealin-HP1 相互作用在协调准确细胞分裂中的关键作用。
