4.7 Article

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

期刊

DEVELOPMENTAL CELL
卷 12, 期 1, 页码 31-43

出版社

CELL PRESS
DOI: 10.1016/j.devcel.2006.11.001

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资金

  1. NATIONAL CENTER FOR RESEARCH RESOURCES [P41RR000862] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM075249] Funding Source: NIH RePORTER
  3. NCI NIH HHS [T32 CA009673, CA09673] Funding Source: Medline
  4. NCRR NIH HHS [RR00862, P41 RR000862] Funding Source: Medline
  5. NIGMS NIH HHS [R01 GM075249, T32 GM007739, GM075249, GM07739] Funding Source: Medline

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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.

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