AURORA B PATHWAY PARTIALLY REGULATES SPINDLE ASSEMBLY

AURORA B 通路部分调节主轴组件

• 批准号: 7954103
• 负责人: Hironori Funabiki
• 金额: $ 0.24万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954103
• 关键词: Antibodies; Binding; Bypass; Cells; Chromatin; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupled; Cytoplasm; Funding; Grant; Institution; Manuscripts; Microtubules; Mitotic; Pathway interactions; Phosphoric Monoester Hydrolases; Phosphotransferases; Process; Proteins; Publishing; Regulation; Research; Research Personnel; Resources; Running; Source; Structure; United States National Institutes of Health; Work; Xenopus; aurora B kinase; borealin; egg; macromolecule; survivin

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. A manuscript describing this work has been published: Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H. Dev Cell. 2007 12(1):31-43.

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