Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA.
Cell Signal. 2012 Aug;24(8):1677-89. doi: 10.1016/j.cellsig.2012.04.014. Epub 2012 Apr 25.
Aurora B kinase forms the enzymatic core of the Chromosomal Passenger Complex (CPC) and is a master regulator of mitosis. Understanding the regulation of Aurora B is critical to illuminate its role in mitosis. INCENP, Survivin and Borealin have all been known to promote Aurora B activation. In this study, we have identified the Aurora A activator protein TPX2 as a novel scaffold and co-activator protein of the CPC. Studies utilizing M-phase Xenopus egg extracts (XEE) revealed that the immunodepletion of endogenous TPX2 from XEE decreases Aurora B-Survivin and Aurora B-INCENP interactions, leading to a consequent reduction in Aurora B activity. Further, residues 138 to 328 of Xenopus TPX2 (TPX2 B) are sufficient to enhance Aurora B-Survivin association and Aurora B kinase activity in vitro. Importantly, experiments with pancreatic cancer cell lines suggest that this mechanism of Aurora B activation by TPX2 is likely to be conserved in human cells. Strikingly, the overexpression of human TPX2 B in HeLa cells causes defects in metaphase chromosome alignment and INCENP localization. Thus, in addition to its already established role as an Aurora A activator, our data support the role of TPX2 as a novel co-activator of Aurora kinase B.
极光 B 激酶构成染色体乘客复合物（CPC）的酶核心，是有丝分裂的主要调节剂。了解极光 B 的调节对于阐明其在有丝分裂中的作用至关重要。INCENP、Survivin 和 Borealin 都被认为能促进 Aurora B 的激活。在这项研究中，我们已经确定 Aurora A 激活蛋白 TPX2 是 CPC 的新型支架和共激活蛋白。利用有丝分裂期爪蟾卵提取物（XEE）的研究表明，从 XEE 中免疫耗竭内源性 TPX2 会减少 Aurora B-Survivin 和 Aurora B-INCENP 相互作用，从而导致 Aurora B 活性降低。此外，爪蟾 TPX2 的 138 到 328 个残基（TPX2 B）足以增强体外 Aurora B-Survivin 结合和 Aurora B 激酶活性。重要的是，对胰腺癌细胞系的实验表明，TPX2 激活 Aurora B 的这种机制可能在人类细胞中保守。引人注目的是，人 TPX2 B 在 HeLa 细胞中的过表达导致中期染色体排列和 INCENP 定位缺陷。因此，除了其作为 Aurora A 激活剂的已有作用外，我们的数据还支持 TPX2 作为 Aurora 激酶 B 的新型共激活因子的作用。
