AURORA B PATHWAY PARTIALLY REGULATES SPINDLE ASSEMBLY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 染色质诱导的纺锤体组装依赖于染色体乘客复合体(CPC)对微管解聚蛋白的调节，该复合体由Incenp、Survivin、Dasra(Borealin)和Aurora B激酶组成，但Aurora B活性的空间调节机制和意义尚不清楚。在这里，我们表明，极光B途径在非洲爪哇卵子提取物的细胞质中被磷酸酶抑制，但它被染色质激活，这是一种Ran不依赖的机制。虽然纺锤体微管组装通常需要依赖于Dasra的染色质结合CPC，但Dasra的这一功能可以通过使用抗Incenp抗体聚集Aurora B-Incenp来绕过，这会刺激结合的复合体之间的自激活。然而，这种染色质非依赖性Aurora B途径的激活促进了中心体微管的组装，并产生了异常的染色体纺锤体样结构。我们认为，染色体上CPC的丰富导致了局部的激酶自激活，这一机制有助于纺锤体组装的空间调节，并可能参与其他有丝分裂过程。

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.