Kelly Alexander E, Sampath Srinath C, Maniar Tapan A, Woo Eileen M, Chait Brian T, Funabiki Hironori
Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10021, USA.
Dev Cell. 2007 Jan;12(1):31-43. doi: 10.1016/j.devcel.2006.11.001.
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.
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控，该复合体由Incenp、Survivin、Dasra（Borealin）和激酶Aurora B组成，但Aurora B活性的空间调控机制及意义仍不清楚。在这里，我们表明，在非洲爪蟾卵提取物的细胞质中，磷酸酶会抑制Aurora B通路，但染色质会通过一种不依赖Ran的机制使其激活。虽然纺锤体微管组装通常需要Dasra依赖的CPC与染色质结合，但通过使用抗Incenp抗体使Aurora B-Incenp聚集，可以绕过Dasra的这一功能，抗Incenp抗体可刺激结合复合物之间的自激活。然而，这种不依赖染色质的Aurora B通路激活会促进中心体微管组装并产生异常的无染色体纺锤体样结构。我们提出，CPC在染色体上的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控，并可能对其他有丝分裂过程也有作用。
