Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly
Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly
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DOI：
10.1016/j.devcel.2006.11.001
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发表时间：
2007-01-01
影响因子：
11.8
通讯作者：
Funabiki, Hironori
中科院分区：
文献类型：
--
作者：
Kelly, Alexander E.;Sampath, Srinath C.;Funabiki, Hironori
染色质诱导的纺锤体组装依赖于由Incenp、Survivin、Dasra （Borealin）和Aurora B激酶组成的染色体客运复合体（CPC）对微管解聚蛋白的调控，但Aurora B活性的空间调控机制和意义尚不清楚。在这里，我们证明了在非洲爪蟾卵提取物的细胞质中，磷酸化酶抑制了Aurora B通路，但它通过一种不依赖于ran的机制被染色质激活。虽然纺锤体微管组装通常需要Dasra依赖的染色质结合CPC，但通过使用抗incenp抗体聚集Aurora B-Incenp可以绕过Dasra的这一功能，这种抗体可以刺激结合复合物之间的自激活。然而，这种不依赖染色质的极光B通路激活促进中心体微管组装并产生异常的染色体纺锤状结构。我们认为CPC的染色体富集导致局部激酶自激活，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。
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.