AURORA B PATHWAY PARTIALLY REGULATES SPINDLE ASSEMBLY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 染色质诱导的纺锤体组装依赖于染色体乘客复合物（CPC）对微管解聚蛋白的调节，所述CPC由Incexp、Survivin、Dasra（Borealin）和激酶Aurora B组成，但是Aurora B活性的空间调节的机制和意义尚不清楚。在这里，我们表明，极光B途径被抑制在非洲爪蟾卵提取物的细胞质中的磷酸酶，但它成为激活染色质通过RAN独立的机制。虽然纺锤体微管组装通常需要CPC的Dasra依赖性染色质结合，但Dasra的这种功能可以通过使用抗Incexp抗体聚集Aurora B-Incexp来绕过，该抗体刺激结合复合物之间的自激活。然而，这种染色质非依赖性极光B途径激活促进中心体微管组装，并产生异常的非染色体纺锤体样结构。我们建议，染色体富集的CPC的结果在当地的激酶自动激活，一种机制，有助于空间调控的纺锤体组装和可能的其他有丝分裂过程。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes. However, such chromatin-independent Aurora B pathway activation promotes centrosomal microtubule assembly and produces aberrant achromosomal spindle-like structures. We propose that chromosomal enrichment of the CPC results in local kinase autoactivation, a mechanism that contributes to the spatial regulation of spindle assembly and possibly to other mitotic processes.