Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly

被引:172
作者
Kelly, Alexander E.
Sampath, Srinath C.
Maniar, Tapan A.
Woo, Eileen M.
Chait, Brian T.
Funabiki, Hironori
机构
[1] Rockefeller Univ, Lab Chromosome & Cell Biol, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10021 USA
[3] Rockefeller Univ, Lab Chromatin Biol, New York, NY 10021 USA
关键词
D O I
10.1016/j.devcel.2006.11.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:31 / 43
页数:13
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